The Commonwealth reimagined 8 November 2022 — 6:00PM TO 7:00PM Anonymous (not verified) 18 October 2022 Chatham House and Online

Ghana’s minister of foreign Affairs, the Hon. Shirley Ayorkor Botchwey, discusses her vision for a modern Commonwealth and how it can evolve and match demands from its members.

The death of HM Queen Elizabeth II has focused attention on the future of the Commonwealth. The Commonwealth is an expanding voluntary organization of 56 independent countries in Africa, Asia, the Americas, Europe, and the Pacific.

Its appeal is increasingly beyond the circle of former British colonies – ex-French colonies Togo and Gabon officially joined in October 2022 and the ex-Portuguese colony, Angola, has applied. The Commonwealth Secretariat, established in 1965, is its main intergovernmental agency, which coordinates and carries out much of the Commonwealth’s work, supported by a network of more than 80 organizations.

King Charles III now heads the Commonwealth, which is focused on shared goals of prosperity, democracy and peace. However, the future of the Commonwealth and its purpose are unclear, and the organization needs to develop a sharper agenda on what its international contribution can be across its 56 state members and their peoples.

The minister discusses key questions including:

• What should a modern Commonwealth look like and how can it best operate?

• How can the organization impact policies and actions at a country level?

• What role will young people play in the future of the Commonwealth?

• How can the organization harness collective resources and technology to tackle major global issues such as climate change?

• Can the issue of mobility and immigration among member states be managed?

Russia’s invasion of Ukraine: How it changed the world 21 February 2023 — 6:00PM TO 7:00PM Anonymous (not verified) 1 February 2023 Chatham House and Online

Chatham House experts examine how the world has changed since 24 February 2022.

Russia’s invasion of Ukraine prompted serious soul-searching about European security, what it means to be European and the futures of the two principal protagonists. However, practical questions have developed throughout the war in surprising ways.

Chatham House is producing a multi-author feature reflecting on seven things Russia’s war has changed in the world. The article assesses the impact of the war one year on, the long-term changes this has catalyzed and unpacks why these changes are significant for the future of international affairs.

This event examines key themes with the research directors who authored the piece. Alliances, national resiliency for both Ukraine and Russia and sanctions are examined including the following questions:

• How did the war change Ukraine?

• What alliances have been forged over the past year? 

• How long can ‘fortress Russia’ weather the storm and what has it revealed about Russia’s integration into the international system? 

• What have countries done to mitigate the impact on supply chains and markets? Who, for example, has been most affected by the grain crisis?

• What have we learnt about Vladimir Putin and Volodymyr Zelensky that we didn’t know before 24 February 2022?

As with all members events, questions from the audience drive the conversation.

Linked article: ‘Seven ways Russia’s war on Ukraine has changed the world’, read the featured piece here.

Read the transcript. 

Chatham House Primer: Social media and democracy 21 March 2023 — 6:00PM TO 6:45PM Anonymous (not verified) 23 February 2023 Chatham House

From the Arab Spring to the 2016 Trump election win, how have democracies benefited and suffered from the impact of social media? 

With social media now a well-entrenched, yet still recent, component of societies, democracies are still grappling with the impact bought about by this new form of communication and promotion.

For all that social media has bought people closer together and brought government, business and civic leaders, it has also been said to have fuelled divisions and hate. Governments and businesses are now drawing battle lines on the legal responsibilities required of social media platforms as we slowly determine the role they play in our society.

This Primer will discuss key questions including:

• What are the current legal responsibilities of social media companies? What sort of laws and regulations must they abide by?
• How are governments looking to change to this?
• How have some countries manipulated social media to monitor and censor their populations?
• Can social media truly tackle harmful and dangerous content?
• Is it possible to combat disinformation and what role should social media platforms play?
• How can we make social media best fit our society in the future?
• How should we govern online space?

A drinks reception will follow this event.

As with all member events, questions from the audience drive the conversation.

The National Institute for Health and Care Excellence (NICE) has recommended that all women with suspected endometriosis be offered an early transvaginal ultrasound scan, even if the pelvic or abdominal examination is normal.In its updated guideline1 on the diagnosis and management of endometriosis, NICE recommends specialist ultrasound as an alternative to magnetic resonance imaging for investigating suspected cases of the condition in secondary care.The updated guideline follows recent reports from both the National Confidential Enquiry into Patient Outcome and Death2 and Endometriosis UK which highlighted problems with delayed diagnoses, partly owing to a lack of awareness among healthcare professionals of the condition and how it presents. Such delays can result in prolonged suffering, ill health, and risks to fertility, the reports warned.Other new and updated recommendations include asking women with suspected endometriosis if any first degree relatives have a history of the condition, and considering neurodiversity when taking into account...

I’m often asked if I miss working in the House of Commons. Of course I do; it’s one of the most amazing places in the world and remains the cockpit of our nation.There are obviously days I miss it more than others, usually around the big national moments. Whatever your view of Kim Leadbeater’s private member’s bill—the Terminally Ill Adults (End of Life) Bill—its second reading this month will be one of those big moments.Kim is a friend of mine, and we spoke before she decided to put her bill forward after it topped the private members’ ballot at the start of the new parliament. My advice was to proceed with great care, to remember that this will take over your career in many ways, and to read the report produced earlier this year by the Health and Social Care Committee, which I chaired, on the subject of assisted dying/assisted...

Concerns are mounting over whether the NHS can meet key performance targets this winter, NHS Providers has said, after a survey of trust leaders highlighted pressure on hospitals, ambulance services, and community and mental health teams.1Over nine in 10 of the leaders who responded (96%) said that they were extremely or moderately concerned about the effect of winter pressures on their trust and local area. The most common reasons for concerns related to financial constraints and staffing provision. The top three greatest risks to the provision of high quality patient care over winter were identified as delayed discharge (57%), social care capacity (49%), and acute care bed capacity (43%).NHS Providers surveyed 171 trust leaders from 118 trusts in September and October, accounting for 56% of the provider sector.Most trust leaders (79%) were worried or very worried about whether their trusts had capacity to meet demand for services over the next...

Undercurrents: Europe's far-right educational institutions Audio bhorton.drupal 8 October 2021

In Hungary, France and Spain, new political movements from the far-right are attempting to reshape their education systems.

Under the supportive eye of Prime Minister Viktor Orbán, the recently established National University of Public Service seeks to embed nationalist illiberal values in a new generation of Hungarian students. Meanwhile in France and Spain, far-right public figure Marion Maréchal has turned away from the electoral politics of the Front Nationale to set up a new conservative research institute, ISSEP.

Both of these developments represent a challenge to the liberal values which underpin the existing international order. To find out more, Ben spoke with Professor Dorit Geva and Dr Felipe Santos, whose recent article in International Affairs considers the implications of this illiberal educational turn. 

Limited expectations as Scholz heads to Kyiv and Moscow Expert comment NCapeling 14 February 2022

After heavy criticism for an initially timid response, the approach of Germany’s new government to the Ukraine crisis is improving as its position on Russia evolves.

Olaf Scholz is a famously quiet and cautious communicator and, as concerns mounted in Washington and London about the possibility of a Russian invasion of Ukraine, the new German chancellor remained silent.

This time his silence reflected the fact that his government was unprepared for its first major foreign policy test, with marked divisions between the SPD and the Greens on how to manage a rapidly deteriorating relationship with Russia.

When he did speak, Scholz caused dismay in several NATO capitals by defending the controversial Nord Stream 2 pipeline. He called it ‘a purely private economic project’ even though the company building the pipeline is a subsidiary of Russia’s state-owned Gazprom.

The absence of crisis management from Berlin was a stark reminder of the gap left by Angela Merkel. Her knowledge of Russia and Ukraine, and her personal experience of dealing with Vladimir Putin, were key assets in 2014 in developing a unified western response to Russia’s annexation of Crimea and its destabilization of south-eastern Ukraine.

Germany has coordinated with its allies

Scholz has prepared the ground carefully for his visits to Kyiv and Moscow, extensively coordinating with NATO allies, such as France and Poland – as part of the Weimar Triangle – and the three Baltic states. His inaugural visit to Washington helped align positions on US-EU efforts to develop an economic deterrent against further Russian intervention in Ukraine.

Scholz has also repeated Merkel’s language from 2014 to signal to Moscow that Germany and its partners are ‘united and determined’ to stand their ground. And he has spoken of Germany’s continuing double strategy of ‘clear announcements’ to Moscow of the price it would pay for further aggression accompanied by a readiness to use all possible channels of dialogue to preserve peace.

The continuation of Germany’s established policy will not surprise Moscow. But under the surface Germany’s discourse on Russia is evolving as the political class internalizes the fact that the current Russian leadership is openly threatening to use military force to impose its will on Ukraine and re-configure Europe’s security arrangements.

Despite deep concerns about Germany’s dependence on Russian gas – more than half of the gas it consumes comes from Russia – there is broad acceptance that Nord Stream 2 cannot go ahead if Russia invades Ukraine. But typically, Scholz has not yet said as much publicly, limiting himself to stating ‘all options are on the table.’

Robert Habeck, Germany’s vice-chancellor as well as economic affairs and climate action minister, says the ‘geopolitical situation’ requires Germany to diversify its gas supplies and infrastructure for importing gas. For years, a strong pro-Russian gas lobby has dominated the thinking of the Economics Ministry and one consequence is the complete absence of facilities to import liquefied natural gas.

The German debate on Russia is shifting

A public debate has also started about weapons deliveries to Ukraine, even though this runs counter to deeply embedded pacifist tendencies in German society. Some MPs, former diplomats, and experts have begun to make the case for Germany to supply weapons to Ukraine so it can exercise its right to self-defence and deter military attack.

Christoph Heusgen, a former long-standing foreign policy adviser in the Federal Chancellery, says Berlin’s decision not to deliver arms to Ukraine to avoid endangering the Minsk peace process requires revision now Moscow has abandoned the path of negotiation.

Despite its mantra that there is no alternative to the Minsk Agreements, Berlin now admits these currently offer no prospect of resolving the war in Donbas because Russia is not prepared to implement them properly.

Other taboos are also being broken inside Germany. Heavyweight left-of-centre Die Zeit published the first results of its investigation into the SPD’s links with Russia and their place in Russia’s channels of influence in Germany. And even the SPD’s Sigmar Gabriel, an outspoken champion of Nord Stream 2 during his time as a government minister, has raised the question of Germany terminating energy imports from Russia if there is a drastic deterioration of the security situation.

Polish-British Belvedere Forum 2022 7 July 2022 TO 8 July 2022 — 12:00PM TO 4:00PM Anonymous (not verified) 13 June 2022 Chatham House and Online

The Belvedere Forum is a leading annual British and Polish dialogue that seeks to strengthen the extensive social, economic and political partnership between the two countries.

Please note this event has reached full in-person capacity. You are welcome to join virtually via the Zoom link: https://chathamhouse.zoom.us/webinar/register/WN_QFwXsXb0RoSt-1ywkuPjfQ  

The video on this page is of the opening remarks from the Belvedere Forum, with addresses from Sir Robin Niblett KCMG, Dr Sławomir Dębski, Prof Zdzisław Krasnodębski, Sir Malcolm Rifkind KCMG QC, Ambassador Anna Clunes CMG OBE, Lord (Tariq) Ahmad of Wimbledon, Min Marcin Przydacz, and Ambassador Piotr Wilczek.

This and other session videos are available to watch on the Belvedere Forum 2022 playlist on YouTube. Photos by Mateusz Jozwiak, Zuzanna Nowak/PISM.

The Belvedere Forum is a leading annual British and Polish bilateral dialogue bringing together a diverse group of actors from civil society, politics, business, academia and NGOs.

It seeks to strengthen and deepen the extensive partnership between the two countries by exploring political, economic, social and cultural issues through debate and discussion.

The forum is an annual event alternating between the UK and Poland. Originally created in 2017 by the governments of the UK and Poland, the forum is now jointly organized by Chatham House and the Polish Institute of International Affairs (PISM) in Warsaw.

The forum brings together a diverse group of actors to debate and discuss not only current British-Polish relations, but also the British and Polish responses to key European and global challenges.

In conversation with Edi Rama, prime minister of Albania 23 March 2023 — 5:30PM TO 6:30PM Anonymous (not verified) 13 March 2023 Chatham House and Online

From migration to Russia and China, how is Albania responding to the geopolitical challenges of today?

In late 2022, the UK government made a pointed remark that many of the illegal migrants attempting to get into the country were from Albania. In response, Albania prime minister Edi Rama replied that targeting Albanians as the cause of Britain’s crime and border problems ‘makes for easy rhetoric but ignores hard fact’. 

This nuanced response demonstrated the challenges and complexities that Albania faces, the same as many other countries. As well as being embroiled in the major challenge of international migration, Albania has suffered from a serious cyber-attack in July 2022 from Iran. Government networks were compromised for a month with Tirana removing the Iranian embassy in the capital.

Then there is the ongoing threat from Russia and China. Nestled in the already volatile Balkans, Albania has been at the heart of international affairs in recent months.

Prime Minister Rama speaks at Chatham House to discuss:

• How is Albania responding to Russian aggression and what is its stance on Ukraine?
• Where does Tirana believe China poses the most serious threat?
• How can countries in Europe best respond to illegal migration and better control the flow of people?
• How is the region of the Western Balkans effected by the war in Ukraine and how can it contribute to the security challenges posed by the war?

As with all member events, questions from the audience drive the conversation.

Review: Rediscovering Milan Kundera’s European tragedy The World Today mhiggins.drupal 28 March 2023

The Czech writer’s 40-year-old essay on the roots of Russia’s empire-building, ‘A Kidnapped West’, reads all too presciently, writes Stefan Auer.

A Kidnapped West: The Tragedy of Central Europe
Milan Kundera, Faber, £10

‘In November 1956, the director of the Hungarian News Agency, shortly before his office was flattened by artillery fire, sent a telex to the entire world with a desperate message announcing that the Russian attack against Budapest had begun. The dispatch ended with these words: “We are going to die for Hungary and for Europe.”’ Thus, Milan Kundera began his 1983 essay for the French journal Le Débat, reflecting on the 1956 Hungarian Uprising.

A seminal essay

The Czech author might well have written a near-identical passage about the fraught hours immediately after Russia’s invasion of Ukraine in 2022. In the event, Russian tanks failed to occupy Kyiv, unlike Budapest in 1956. Nevertheless, Faber has chosen this moment, 40 years later, to republish Kundera’s seminal essay on Europe and Russian aggression in its original translation for the New York Review of Books by Edmund White. How salient are its observations today?

The essay’s original French title, ‘Un Occident kidnappé ou la tragédie de l’Europe centrale’ (The Kidnapped West, or the Tragedy of Central Europe), described the fate of Hungary, Czechoslovakia in 1968 and, to an extent, Poland in 1980-81 at the hands of the Soviet Union. Owing to the Cold War division of Europe, the countries of Central Europe were denied their true destiny, Kundera thought, to be an integral part of the liberal, democratic West. Kundera himself fled Czechoslovakia for France in 1975.

The author of The Unbearable Lightness of Being might no longer be as well-known as he was at the height of his fame in the 1980s, but his novels and essays still deserve attention. So, it is pleasing to see Kundera’s masterpiece republished, even as it is awful to witness the enduring relevance of the questions it raises.

What did the Hungarian journalist mean when he declared his willingness to die for Europe, Kundera asked? That ‘Russians, in attacking Hungary, were attacking Europe itself. He was ready to die so that Hungary might remain Hungary and European’. The journalist did indeed die in the uprising.

It is a line that President Volodymyr Zelenskyy and his supporters abroad have echoed time and again: that Ukrainian soldiers are not just dying for their country, they are dying for Europe at large.

The ‘tragedy’ in Kundera’s essay was that the West didn’t care. ‘Europe hasn’t noticed the disappearance of its cultural home,’ Kundera wrote, ‘because Europe no longer perceives its unity as a cultural unity.’

In other words, as the cultural sphere in Central Europe continued to defy the political restrictions imposed by the Soviet empire, it embodied the western values of freedom and democracy more than the West itself did. The extent to which this analysis remains relevant today will prove decisive for Europe’s future.

As timely as ever

Kundera’s essay is as timely as ever but in ways that both vindicate and challenge his key arguments. His suspicion of Russia has been validated. His frustration about the indifference of the West less so. But the true tragedy of Ukraine would be if the West has not changed sufficiently. So far, the West appears to be doing enough to enable Ukraine to defend itself, but not enough to defeat the aggressor.

Faber has made an excellent decision in combining The Tragedy of Central Europe with a lesser-known text by Kundera: his 1967 speech to the Czech Writers’ Congress given the year before the ill-fated Prague Spring. In it, Kundera addressed what was to become a lifelong preoccupation: the fate of small nations. ‘For Czechs’, Kundera wrote, ‘nothing has ever constituted an indisputable possession – neither their language nor their belonging to Europe.’

Rather than reflecting the size of its territory or population, a small nation ‘is one whose very existence can be put in question at any moment; a small nation can disappear, and it knows it.’ In this way Ukraine, Europe’s largest country, apart from Russia, is fighting to avoid the fate of Kundera’s ‘small nation’.

Historically, the ‘small’ nations of Central Europe were threatened by both Germany and Russia. But after the Second World War, the threat was from the Soviet Union, which for Kundera was indistinguishable from Russia (tacitly including Ukraine). In its expansiveness, Russia was the opposite of Central Europe. While the latter was based on the principle of ‘the greatest variety within the smallest space’, the former represented ‘the smallest variety within the greatest space’.

In this sense, authoritarian communism was the fulfilment of Russian history, Kundera argued, writing that ‘Russian communism vigorously reawakened Russia’s old anti-western obsessions and turned it brutally against Europe’. Vladimir Putin’s Russia appears to build on these same pernicious impulses.

Kundera was widely criticized for observations in his essay that smack of civilizational racism (including by me) describing Russians as fundamentally different from us: ‘Russia knows another (greater) dimension of disaster, another image of space (a space so immense that entire nations are swallowed up in it), another sense of time (slow and patient), another way of laughing, living, and dying’.

Independent Thinking: Sweden, Finland, and NATO Audio NCapeling 31 March 2023

Episode 21 of our weekly podcast examines the latest developments relating to Sweden and Finland’s proposed accession to NATO.

The Hungarian parliament has finally ratified Finland’s membership to the NATO alliance, two weeks after President Erdogan in Turkey gave his seal of approval following a meeting with the Finnish president.

Sweden however remains trapped in limbo, with both Turkey and Hungary delaying Stockholm’s membership and Erdogan in particular asking for more concessions.

The panel discusses why Turkey and Hungary took issue with Sweden and Finland, what the strategic situation in the Baltic looks like now with only Finland joining NATO, and the challenges facing Sweden amid its fraught ties with President Erdogan.

We also look ahead to Turkey’s presidential election in May as recent opinion polls point to a neck-and-neck race, with some polls even showing President Erdogan falling behind the opposition. The panel examines what the sentiment is like in Turkey ahead of the election, and how the world would respond if there was a change in power in Ankara for the first time in 20 years.

Joining Bronwen Maddox on the podcast this week is Henri Vanhanen, research fellow with the Finnish Institute of International Affairs, and Galip Dalay, associate fellow with our Middle East and North Africa programme.

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.

C-X-C motif chemokine receptor 4 (CXCR4)–directed imaging has gained clinical interest in aiding clinical diagnostics in primary aldosteronism (PA). We retrospectively evaluated the feasibility of CXCR4-directed scintigraphy using the novel CXCR-4 ligand [^99mTc]Tc-pentixatec in patients with PA. Methods: Six patients (mean age ± SD, 49 ± 15 y) underwent CXCR4-directed scintigraphy (including planar imaging and SPECT/CT) 30, 120, and 240 min after injection of 435 ± 50 MBq of [^99mTc]Tc-pentixatec. Adrenal CXCR4 expression was analyzed by calculating lesion-to-contralateral ratios (LCRs). Imaging results were correlated to clinical information. Histopathology and clinical follow-up served as the standard of reference. Results: Three subjects showed lateralization of adrenal tracer accumulation, with a mean maximum lesion-to-contralateral ratio of 1.65 (range, 1.52–1.70), which correlated with morphologic findings on CT. One individual underwent adrenalectomy and presented with complete biochemical and clinical remission at follow-up. Histopathologic workup confirmed unilateral aldosterone-producing adenoma. Conclusion: [^99mTc]Tc-pentixatec scintigraphy with SPECT in patients with PA is feasible and might offer a valuable alternative to CXCR4-directed imaging with [⁶⁸Ga]Ga-pentixafor PET.

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post–myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with ¹⁸F for imaging by PET and characterized its in vivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with ¹⁸F a quinazolinone derivative ([¹⁸F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and in vivo and ex vivo specificity of [¹⁸F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [¹⁸F]LCE470 was determined by time–activity curve and SUV analysis in 3 regions of the left ventricle—area of infarct, territory served by the left circumflex coronary artery, and remote myocardium—over a period of 1.5 y. Changes in cardiac perfusion were tracked by [¹³N]NH₃ PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [¹⁸F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [¹⁸F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [¹⁸F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [¹⁸F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.

Mutations of p53 protein occur in over half of all cancers, with profound effects on tumor biology. We present the first—to our knowledge—method for noninvasive visualization of p53 in tumor tissue in vivo, using SPECT, in 3 different models of cancer. Methods: Anti-p53 monoclonal antibodies were conjugated to the cell-penetrating transactivator of transcription (TAT) peptide and a metal ion chelator and then radiolabeled with ¹¹¹In to allow SPECT imaging. ¹¹¹In-anti-p53-TAT conjugates were retained longer in cells overexpressing p53-specific than non–p53-specific ¹¹¹In-mIgG (mouse IgG from murine plasma)-TAT controls, but not in null p53 cells. Results: In vivo SPECT imaging showed enhanced uptake of ¹¹¹In-anti-p53-TAT, versus ¹¹¹In-mIgG-TAT, in high-expression p53^R175H and medium-expression wild-type p53 but not in null p53 tumor xenografts. The results were confirmed in mice bearing genetically engineered KPC mouse–derived pancreatic ductal adenocarcinoma tumors. Imaging with ¹¹¹In-anti-p53-TAT was possible in KPC mice bearing spontaneous p53^R172H pancreatic ductal adenocarcinoma tumors. Conclusion: We demonstrate the feasibility of noninvasive in vivo molecular imaging of p53 in tumor tissue using a radiolabeled TAT-modified monoclonal antibody.

Preclinical data have shown that ¹⁶¹Tb-labeled peptides targeting the somatostatin receptor are therapeutically more effective for peptide receptor radionuclide therapy than are their ¹⁷⁷Lu-labeled counterparts. To further substantiate this enhanced therapeutic effect, we performed cellular dosimetry to quantify the absorbed dose to the cell nucleus and compared dose–response curves to evaluate differences in relative biological effectiveness in vitro. Methods: CA20948 cell survival was assessed after treatment with [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTATATE (agonist) and with [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTA-LM3 (antagonist) via a clonogenic assay. Cell binding, internalization, and dissociation assays were performed up to 7 d to acquire time-integrated activity coefficients. Separate S values for each type of particle emission (Auger/internal conversion [IC] electrons and β^– particles) were computed via Monte Carlo simulations, while considering spheric cells. Once the absorbed dose to the cell nucleus was calculated, survival curves were fitted to the appropriate linear or linear-quadratic model and corresponding relative biological effectiveness was evaluated. Results: Although the radiopeptide uptake was independent of the radionuclide, [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 delivered a 3.6 and 3.8 times higher dose to the nucleus, respectively, than their ¹⁷⁷Lu-labeled counterparts on saturated receptor binding. This increased nucleus-absorbed dose was mainly due to the additional emission of IC and not Auger electrons by ¹⁶¹Tb. When activity concentrations were considered, both [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 showed a lower survival fraction than did labeling with ¹⁷⁷Lu. When the absorbed dose to the nucleus was considered, no significant difference could be observed between the dose–response curves for [¹⁶¹Tb]Tb- and [¹⁷⁷Lu]Lu-DOTATATE. [¹⁶¹Tb]Tb-DOTA-LM3 showed a linear-quadratic dose response, whereas [¹⁶¹Tb]Tb-DOTATATE showed only a linear dose response within the observed dose range, suggesting additional cell membrane damage by Auger electrons. Conclusion: The IC, rather than Auger, electrons emitted by ¹⁶¹Tb resulted in a higher absorbed dose to the cell nucleus and lower clonogenic survival for [¹⁶¹Tb]Tb-DOTATATE and [¹⁶¹Tb]Tb-DOTA-LM3 than for the ¹⁷⁷Lu-labeled analogs. In contrast, [¹⁶¹Tb]Tb-DOTATATE showed no higher dose response than [¹⁷⁷Lu]Lu-DOTATATE, whereas for [¹⁶¹Tb]Tb-DOTA-LM3 an additional quadratic response was observed. Because of this quadratic response, potentially caused by cell membrane damage, [¹⁶¹Tb]Tb-DOTA-LM3 is a more effective radiopeptide than [¹⁶¹Tb]Tb-DOTATATE for labeling with ¹⁶¹Tb.

Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic - and β-emitting isotope ¹⁷⁷Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Methods: Gemini was synthesized by linking 2 S-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [¹⁷⁷Lu]Lu-Gemini was prepared with no-carrier-added ¹⁷⁷LuCl₃ to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-¹⁷⁷Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [¹⁷⁷Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [¹⁷⁷Lu]Lu-S-2-(4-aminobenzyl)-DOTA ([¹⁷⁷Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [¹⁷⁷Lu]Lu-Gemini) in mouse models. Results: Initial in vivo studies showed that [¹⁷⁷Lu]Lu-Gemini behaved similarly to [¹⁷⁷Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [¹⁷⁷Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [¹⁷⁷Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor–to–normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [¹⁷⁷Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [¹⁷⁷Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [¹⁷⁷Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [¹⁷⁷Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). Conclusion: We have developed a bivalent DOTA-radiohapten, [¹⁷⁷Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [¹⁷⁷Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [¹⁷⁷Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered ¹⁷⁷Lu activity while still achieving high TIs for both the blood (>100) and the kidneys (>30).

Fibroblast activation protein (FAP) is abundantly expressed in the stroma of most human solid tumors. Clinical-stage radiolabeled FAP ligands are increasingly used as tools for the detection of various cancer lesions. To unleash the full therapeutic potential of FAP-targeting agents, ligands need to remain at the tumor site for several days after administration. We recently described the discovery of OncoFAP, a high-affinity small organic ligand of FAP with a rapid accumulation in tumors and low uptake in healthy tissues in cancer patients. Trimerization of OncoFAP provided a derivative (named TriOncoFAP, or OncoFAP-23) with improved FAP affinity. In this work, we evaluated the tissue biodistribution profile and the therapeutic performance of OncoFAP-23 in tumor-bearing mice. Methods: OncoFAP-23 was radiolabeled with the theranostic radionuclide ¹⁷⁷Lu. Preclinical experiments were conducted on mice bearing SK-RC-52.hFAP (BALB/c nude mice) or CT-26.hFAP (BALB/c mice) tumors. ¹⁷⁷Lu-OncoFAP and ¹⁷⁷Lu-FAP-2286 were included in the biodistribution study as controls. Toxicologic evaluation was performed on Wistar rats and CD1 mice by injecting high doses of OncoFAP-23 or its cold-labeled counterpart, respectively. Results: ¹⁷⁷Lu-OncoFAP-23 emerged for its best-in-class biodistribution profile, high and prolonged tumor uptake (i.e., ~16 percentage injected dose/g at 96 h), and low accumulation in healthy organs, which correlates well with its potent single-agent anticancer activity at low levels of administered radioactivity. Combination treatment with the tumor-targeted interleukin 2 (L19-IL2, a clinical-stage immunocytokine) further expands the therapeutic window of ¹⁷⁷Lu-OncoFAP-23 by potentiating its in vivo antitumor activity. Proteomics studies revealed a potent tumor-directed immune response on treatment with the combination. OncoFAP-23 and ^natLu-OncoFAP-23 exhibited a favorable toxicologic profile, without showing any side effects or signs of toxicity. Conclusion: OncoFAP-23 presents enhanced tumor uptake and tumor retention and low accumulation in healthy organs, findings that correspond to a strongly improved in vivo antitumor efficacy. The data presented in this work support the clinical development of ¹⁷⁷Lu-OncoFAP-23 for the treatment of FAP-positive solid tumors.

To date, the imaging and diagnosis of hepatocellular carcinoma (HCC) rely on CT/MRI, which have well-known limitations. Glypican-3 (GPC3) is a cell surface receptor highly expressed by HCC but not by normal or cirrhotic liver tissue. Here we report initial clinical results of GPC3-targeted PET imaging with [⁶⁸Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. Methods: [⁶⁸Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with ⁶⁸Ga from a ⁶⁸Ge/⁶⁸Ga generator and heating at 90°C for 10 min followed by sterile filtration. After administration of [⁶⁸Ga]Ga-RAYZ-8009, a dynamic or static PET/CT scan was acquired between 45 min and 4 h after administration. Radiotracer uptake was measured by SUVs for the following tissues: suspected or actual HCC or hepatoblastoma lesions, non–tumor-bearing liver, renal cortex, blood pool in the left ventricle, and gastric fundus. Additionally, tumor–to–healthy-liver ratios (TLRs) were calculated. Results: Twenty-four patients (5 patients in the dynamic protocol; 19 patients in the static protocol) were scanned. No adverse events occurred. Two patients had no lesion detected and did not have HCC during follow-up. In total, 50 lesions were detected and analyzed. The mean SUV_max of these lesions was 19.6 (range, 2.7–95.3), and the mean SUV_mean was 10.1 (range, 1.0–49.2) at approximately 60 min after administration. Uptake in non–tumor-bearing liver and blood pool rapidly decreased over time and became negligible 45 min after administration (mean SUV_mean, <1.6), with a continuous decline to 4 h after administration (mean SUV_mean, 1.0). The opposite was observed for HCC lesions, for which SUVs and TLRs continuously increased for up to 4 h after administration. In individual lesion analysis, TLR was the highest between 60 and 120 min after administration. Uptake in the gastric fundus gradually increased for up to 45 min (to an SUV_max of 31.3) and decreased gradually afterward. Conclusion: [⁶⁸Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [⁶⁸Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted.

Our purpose was to prospectively assess the distribution of NETPET scores in well-differentiated (WD) grade 2 and 3 gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and to determine the impact of the NETPET score on clinical management. Methods: This single-arm, institutional ethics review board–approved prospective study included 40 patients with histologically proven WD GEP NETs. ⁶⁸Ga-DOTATATE PET and ¹⁸F-FDG PET were performed within 21 d of each other. NETPET scores were evaluated qualitatively by 2 reviewers, with up to 10 marker lesions selected for each patient. The quantitative parameters that were evaluated included marker lesion SUV_max for each tracer; ¹⁸F-FDG/⁶⁸Ga-DOTATATE SUV_max ratios; functional tumor volume (FTV) and metabolic tumor volume (MTV) on ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET, respectively; and FTV/MTV ratios. The treatment plan before and after ¹⁸F-FDG PET was recorded. Results: There were 22 men and 18 women (mean age, 60.8 y) with grade 2 (n = 24) or grade 3 (n = 16) tumors and a mean Ki-67 index of 16.1%. NETPET scores of P0, P1, P2A, P2B, P3B, P4B, and P5 were documented in 2 (5%), 5 (12.5%), 5 (12.5%) 20 (50%), 2 (5%), 4 (10%), and 2 (5%) patients, respectively. No association was found between the SUV_max of target lesions on ⁶⁸Ga-DOTATATE and the SUV_max of target lesions on ¹⁸F-FDG PET (P = 0.505). ¹⁸F-FDG/⁶⁸Ga-DOTATATE SUV_max ratios were significantly lower for patients with low (P1–P2) primary NETPET scores than for those with high (P3–P5) primary NETPET scores (mean ± SD, 0.20 ± 0.13 and 1.68 ± 1.44, respectively; P < 0.001). MTV on ¹⁸F-FDG PET was significantly lower for low primary NETPET scores than for high ones (mean ± SD, 464 ± 601 cm³ and 66 ± 114 cm³, respectively; P = 0.005). A change in the type of management was observed in 42.5% of patients after ¹⁸F-FDG PET, with the most common being a change from systemic therapy to peptide receptor radionuclide therapy and from debulking surgery to systemic therapy. Conclusion: There was a heterogeneous distribution of NETPET scores in patients with WD grade 2 and 3 GEP NETs, with more than 1 in 5 patients having a high NETPET score and a frequent change in management after ¹⁸F-FDG PET. Quantitative parameters including ¹⁸F-FDG/⁶⁸Ga-DOTATATE SUV_max ratios in target lesions and FTV/MTV ratios can discriminate between patients with high and low NETPET scores.

Our objective is to explore quantitative imaging markers for early prediction of treatment response in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) undergoing [¹⁷⁷Lu]Lu-DOTATATE therapy. By doing so, we aim to enable timely switching to more effective therapies in order to prevent time-resource waste and minimize toxicities. Methods: Patients diagnosed with unresectable or metastatic, progressive, well-differentiated, receptor-positive GEP-NETs who received 4 sessions of [¹⁷⁷Lu]Lu-DOTATATE were retrospectively selected. Using SPECT/CT images taken at the end of treatment sessions, we counted all visible tumors and measured their largest diameters to calculate the tumor burden score (TBS). Up to 4 target lesions were selected and semiautomatically segmented. Target lesion peak counts and spleen peak counts were measured, and normalized peak counts were calculated. Changes in TBS (TBS) and changes in normalized peak count (nPC) throughout treatment sessions in relation to the first treatment session were calculated. Treatment responses were evaluated using third-month CT and were binarized as progressive disease (PD) or non-PD. Results: Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in TBS_second-first, TBS_third-first, and TBS_fourth-first (where second-first, third-first, and fourth-first denote scan number between the second and first, third and first, and fourth and first [¹⁷⁷Lu]Lu-DOTATATE treatment cycles), respectively) between the PD and non-PD groups (median, 0.043 vs. –0.049, 0.08 vs. –0.116, and 0.109 vs. –0.123 [P = 0.023, P = 0.002, and P < 0.001], respectively). nPC_second-first showed significant group differences (mean, –0.107 vs. –0.282; P = 0.033); nPC_third-first and nPC_fourth-first did not reach statistical significance (mean, –0.122 vs. –0.312 and –0.183 vs. –0.405 [P = 0.117 and 0.067], respectively). At the optimal threshold, TBS_fourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. TBS_second-first and TBS_third-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. nPC_second-first, nPC_third-first, and nPC_fourth-first showed AUCs of 0.764, 0.693, and 0.679; sensitivities of 71.4%, 71.4%, and 100%; and specificities of 75%, 70%, and 35%, respectively. Conclusion: TBS and nPC can predict [¹⁷⁷Lu]Lu-DOTATATE response by the second treatment session.

Unspecific bone uptake (UBU) related to [¹⁸F]PSMA-1007 PET/CT imaging represents a clinical challenge. We aimed to assess whether a combination of clinical, biochemical, and imaging parameters could predict skeletal metastases in patients with [¹⁸F]PSMA-1007 bone focal uptake, aiding in result interpretation. Methods: We retrospectively analyzed [¹⁸F]PSMA-1007 PET/CT performed in hormone-sensitive prostate cancer (PCa) patients at 3 tertiary-level cancer centers. A fourth center was involved in performing an external validation. For each, a volume of interest was drawn using a threshold method to extract SUV_max, SUV_mean, PSMA tumor volume, and total lesion PSMA. The same volume of interest was applied to CT images to calculate the mean Hounsfield units (HU_mean) and maximum Hounsfield units. Clinical and laboratory data were collected from electronic medical records. A composite reference standard, including follow-up histopathology, biochemistry, and imaging data, was used to distinguish between PCa bone metastases and UBU. PET readers with less (n = 2) or more (n = 2) experience, masked to the reference standard, were asked to visually rate a subset of focal bone uptake (n = 178) as PCa metastases or not. Results: In total, 448 bone [¹⁸F]PSMA-1007 focal uptake specimens were identified in 267 PCa patients. Of the 448 uptake samples, 188 (41.9%) corresponded to PCa metastases. Ongoing androgen deprivation therapy at PET/CT (P < 0.001) with determination of SUV_max (P < 0.001) and HU_mean (P < 0.001) independently predicted bone metastases. A composite prediction score, the bone uptake metastatic probability (BUMP) score, achieving an area under the receiver-operating-characteristic curve (AUC) of 0.87, was validated through a 10-fold internal and external validation (n = 89 bone uptake, 51% metastatic; AUC, 0.92). The BUMP score’s AUC was significantly higher than that of HU_mean (AUC, 0.62) and remained high among lesions with HU_mean in the first tertile (AUC, 0.80). A decision-curve analysis showed a higher net benefit with the score. Compared with the visual assessment, the BUMP score provided added value in terms of specificity in less-experienced PET readers (88% vs. 54%, P < 0.001). Conclusion: The BUMP score accurately distinguished UBU from bone metastases in PCa patients with [¹⁸F]PSMA-1007 focal bone uptake at PET imaging, offering additional value compared with the simple assessment of the osteoblastic CT correlate. Its use could help clinicians interpret imaging results, particularly those with less experience, potentially reducing the risk of patient overstaging.

Single-domain antibodies (sdAbs) demonstrate favorable pharmacokinetic profiles for molecular imaging applications. However, their renal excretion and retention are obstacles for applications in targeted radionuclide therapy (TRT). Methods: Using a click-chemistry–based pretargeting approach, we aimed to reduce kidney retention of a fibroblast activation protein α (FAP)–targeted sdAb, 4AH29, for ¹⁷⁷Lu-TRT. Key pretargeting parameters (sdAb-injected mass and lag time) were optimized in healthy mice and U87MG (FAP⁺) xenografts. A TRT study in a pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft (PDX) model was performed as a pilot study for sdAb-based pretargeting applications. Results: Modification of 4AH29 with trans-cyclooctene (TCO) moieties did not modify the sdAb pharmacokinetic profile. A 200-µg injected mass of 4AH29-TCO and an 8-h lag time for the injection of [¹⁷⁷Lu]Lu-DOTA-PEG₇-tetrazine resulted in the highest kidney therapeutic index (2.0 ± 0.4), which was 5-fold higher than that of [¹⁷⁷Lu]Lu-DOTA-4AH29 (0.4 ± 0.1). FAP expression in the tumor microenvironment was validated in a PDAC PDX model with both immunohistochemistry and PET/CT imaging. Mice treated with the pretargeting high-activity approach (4AH29-TCO + [¹⁷⁷Lu]Lu-DOTA-PEG₇-tetrazine; 3 x 88 MBq, 1 injection per week for 3 wk) demonstrated prolonged survival compared with the vehicle control and conventionally treated ([¹⁷⁷Lu]Lu-DOTA-4AH29; 3 x 37 MBq, 1 injection per week for 3 wk) mice. Mesangial expansion was reported in 7 of 10 mice in the conventional cohort, suggesting treatment-related kidney morphologic changes, but was not observed in the pretargeting cohort. Conclusion: This study validates pretargeting to mitigate sdAbs’ kidney retention with no observation of morphologic changes on therapy regimen at early time points. Clinical translation of click-chemistry–based pre-TRT is warranted on the basis of its ability to alleviate toxicities related to biovectors’ intrinsic pharmacokinetic profiles. The absence of representative animal models with extensive stroma and high FAP expression on cancer-associated fibroblasts led to a low mean tumor-absorbed dose even with high injected activity and consequently to modest survival benefit in this PDAC PDX.

Neoadjuvant therapy in patients with locally advanced rectal cancer (LARC) has achieved good pathologic complete response (pCR) rates, potentially eliminating the need for surgical intervention. This study investigated preoperative methods for predicting pCR after neoadjuvant short-course radiotherapy (SCRT) combined with immunochemotherapy. Methods: Treatment-naïve patients with histologically confirmed LARC were enrolled from February 2023 to July 2023. Before surgery, the patients received neoadjuvant SCRT followed by 2 cycles of capecitabine and oxaliplatin plus camrelizumab. ⁶⁸Ga-labeled fibroblast activation protein inhibitor ([⁶⁸Ga]Ga-FAPI-04) PET/MRI, [¹⁸F]FDG PET/CT, and contrast-enhanced MRI were performed before treatment initiation and before surgery in each patient. PET and MRI features and the size and number of lesions were also collected from each scan. Each parameter’s sensitivity, specificity, and diagnostic cutoff were derived via receiver-operating-characteristic curve analysis. Results: Twenty eligible patients (13 men, 7 women; mean age, 60.2 y) were enrolled and completed the entire trial, and all patients had proficient mismatch repair or microsatellite-stable LARC. A postoperative pCR was achieved in 9 patients (45.0%). In the visual evaluation, both [⁶⁸Ga]Ga-FAPI-04 PET/MRI and [¹⁸F]FDG PET/CT were limited to forecasting pCR. Contrast-enhanced MRI had a low sensitivity of 55.56% to predict pCR. In the quantitative evaluation, [⁶⁸Ga]Ga-FAPI-04 change in SUL_peak percentage, where SUL_peak is SUV_peak standardized by lean body mass, had the largest area under the curve (0.929) with high specificity (sensitivity, 77.78%; specificity, 100.0%; cutoff, 63.92%). Conclusion: [⁶⁸Ga]Ga-FAPI-04 PET/MRI is a promising imaging modality for predicting pCR after SCRT combined with immunochemotherapy. The SUL_peak decrease exceeding 63.92% may provide valuable guidance in selecting patients who can forgo surgery after neoadjuvant therapy.

Understanding which patients with human epidermal growth factor receptor 2 (HER2)–negative or –low metastatic breast cancer (MBC) benefit from HER2-targeted strategies is urgently needed. We assessed the whole-body heterogeneity of HER2 expression on ⁸⁹Zr-trastuzumab PET (HER2 PET) and the diagnostic performance of HER2 PET in a large series of patients, including HER2-negative and -low MBC. Methods: In the IMPACT-MBC study, patients with newly diagnosed and nonrapidly progressive MBC of all subtypes were included. Metastasis HER2 status was determined by immunohistochemistry and in situ hybridization.⁸⁹Zr-trastuzumab uptake was quantified as SUV_max and SUV_mean. HER2 immunohistochemistry was related to the quantitative ⁸⁹Zr-trastuzumab uptake of all metastases and corresponding biopsied metastasis, uptake heterogeneity, and qualitative scan evaluation. A prediction algorithm for HER2 immunohistochemistry positivity based on uptake was developed. Results: In 200 patients, ⁸⁹Zr-trastuzumab uptake was quantified in 5,163 metastases, including 186 biopsied metastases. With increasing HER2 immunohistochemistry status, uptake was higher (geometric mean SUV_max of 7.0, 7.6, 7.3, and 17.4 for a HER2 immunohistochemistry score of 0, 1, 2, or 3+, respectively; P < 0.001). High uptake exceeding 14.6 (90th percentile) was observed in one third of patients with a HER2-negative or -low metastasis biopsy. The algorithm performed best when lesion site and size were incorporated (area under the curve, 0.86; 95% CI, 0.79–0.93). Conclusion: HER2 PET had good diagnostic performance in MBC, showing considerable whole-body HER2 heterogeneity and uptake above background in HER2-negative and -low MBC. This provides novel insights into HER2-negative and -low MBC compared with standard HER2 immunohistochemistry on a single biopsy.

Following early acceptance by urologists, the use of surgical robotic platforms is rapidly spreading to other surgical fields. This empowerment of surgical perception via robotic advances occurs in parallel to developments in intraoperative molecular imaging. Convergence of these efforts creates a logical incentive to advance the decades-old image-guided robotics paradigm. This yields new radioguided surgery strategies set to optimally exploit the symbiosis between the growing clinical translation of robotics and molecular imaging. These strategies intend to advance surgical precision by increasing dexterity and optimizing surgical decision-making. In this state-of-the-art review, topic-related developments in chemistry (tracer development) and engineering (medical device development) are discussed, and future scientific robotic growth markets for molecular imaging are presented.

Can Cyprus Be Reunified? 18 July 2018 — 12:30PM TO 1:30PM Anonymous (not verified) 29 June 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

The latest round of Cyprus peace negotiations to resolve the Cypriot issue broke down in Crans-Montana, Switzerland in July 2017. The speaker will offer the Turkish Cypriot perspective on future developments to reunifying the divided island.

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

A Credit-fuelled Economic Recovery Stores Up Trouble for Turkey Expert comment sysadmin 17 February 2020

Turkey is repeating the mistakes that led to the 2018 lira crisis and another freefall for the currency may not be far off.

Since the 2018 economic crisis, when the value of the lira plummeted and borrowing costs soared, Turkey’s economy has achieved a miraculous ‘V-shaped’ economic recovery from a recession lasting three quarters to a return back to quarterly growth above 1 per cent in the first three months of 2019.

But this quick turnaround has been built on vast amounts of cheap credit used to re-stimulate a consumption and construction boom. This so-called ‘triple C’ economy generated a rapid growth spurt akin to a modestly able professional sprinter injected with steroids.

This has made the currency vulnerable. The lira has steadily depreciated by 11 per cent against the US dollar since the beginning of 2019 and crossed the rate of 6 lira versus the US dollar on 7 February. And there are further warning signs on the horizon.

Credit bonanza

Statistics reveal that Turkish domestic credit grew by around 13 per cent on average throughout 2019. The credit bonanza is still ongoing. Mortgage-backed home sales jumped by a record high of 600 per cent last December alone and the 2019 budget deficit catapulted by 70 per cent due to higher government spending.

Turkey’s central bank fuelled this credit expansion by cutting interest rates aggressively to below inflation and, since the start of this year, purchasing lira-denominated bonds equivalent to around one-third of total acquisitions last year to push yields lower.

Equally, it has linked bank lending to reserve requirements – the money that banks have to keep at the central bank – to boost borrowings via state and private banks. Banks with a ‘real’ loan growth (including inflation) of between 5 and 15 per cent enjoy a 2 per cent reserve ratio on most lira deposits, which authorities adjusted from an earlier band of 10-20 per cent that did not consider double-digit inflation.

Cumulatively, bond purchases (effectively quantitative easing) and reserve management policies have also contributed to eased credit conditions.

Commercial banks have also reduced deposit rates on lira accounts to less than inflation to encourage consumption over saving. Together with low lending rates, the boost to the economy has flowed via mortgages, credit card loans, vehicle leasing transactions and general business borrowings.

Accordingly, stimulus is at the forefront of the government’s economic approach, as it was in 2017 and 2018. It does not seem to be implementing structural change to re-orient growth away from consumption towards productivity.

In addition, governance is, again, a central issue. President Recep Tayyip Erdogan’s near total monopolization of policymaking means he guides all domestic and external policies. He forced out the previous central bank governor, Murat Cetinkaya, in July 2019 because he did not share the president’s desire for an accelerated pace of interest rate reductions.

New challenges

Despite the similarities, the expected future financial turbulence will be materially different from its 2018 predecessor in four crucial respects.

Firstly, foreign investors will only be marginally involved. Turkey has shut out foreign investors since 2018 from lira-denominated assets by restricting lira swap arrangements. Unsurprisingly, the non-resident holdings of lira bonds has plummeted from 20 per cent in 2018 to less than 10 per cent today.

Secondly, the Turkish government has recently introduced indirect domestic capital controls by constraining most commercial transactions to the lira rather than to the US dollar or euro to reduce foreign currency demand in light of short-term external debt obligations of $191 billion.

Thirdly, the Turkish state banks are intervening quite regularly to soften Lira volatility, thereby transitioning from a ‘free float’ to a ‘managed float’. So far, they have spent over $37 billion over the last two years in a futile effort to buttress the lira. This level of involvement in currency markets cannot be maintained.

Fourthly, the Turkish state is being far more interventionist in the Turkish stock exchange and bond markets to keep asset prices elevated. Government-controlled local funds have participated in the Borsa Istanbul and state banks in sovereign debt to sustain rallies or reverse a bear market.

All these measures have one running idea: exclude foreign investors and no crisis will recur. Yet, when the credit boom heads to a downturn sooner or later, Turks will probably escalate lira conversions to US dollars; 51 per cent of all Turkish bank deposits are already dollar-denominated and the figure is still rising.

If Turkey’s limited foreign reserves cannot satisfy the domestic dollar demand, the government may have to impose comprehensive capital controls and allow for a double digit depreciation in the value of the lira to from its current level, with significant repercussions on Turkey’s political stability and economic climate.

To avoid this scenario, it needs to restore fiscal and monetary prudence, deal the with the foreign debt overhang in the private sector and focus on productivity-improving economic and institutional reforms to gain the confidence of global financial markets and Turks alike.

Turkey Needs Radical New Direction to Save the Economy Expert comment NCapeling 23 November 2020

Turkey should emulate the reformist approach it adopted after the 2001 crisis to prevent an economic and financial breakdown - but this looks highly unlikely.

Although Ankara has witnessed what appears to be an abrupt change of its top economic team with two fresh appointments to key positions – Naci Ağbal as governor of the central bank and Lütfi Elvan as finance and treasury minister – a cardinal rule of thumb in Turkish politics is that the more drama one sees, the less policy change there will actually be.

Financial markets reacted positively to the moves in the expectation they will signal a change of Turkey’s overall economic approach, but the reality is Turkish president Recep Tayyip Erdoğan is simply putting loyalists into key bureaucratic positions to help ensure the primary role of these functions becomes ‘selling’ his policies more effectively, rather than altering them.

The hope from the markets – which saw the beleaguered Turkish lira appreciate against the US dollar at the news – is that Turkey adopts substantial interest rate increases as well as measures to repress liquidity expansion in order to temper its controversial so-called ‘Triple C’ approach of using cheap credit to stimulate growth with an unsustainable consumption and construction boom.

But instead, Erdoğan’s declaration after the appointments were made indicates the new restrictions in which they will now operate, saying ‘we are in a historic struggle against those who want to force Turkey into modern capitulations through the shackles of interest rates, foreign exchange rates and inflation’.

Learn from past successes

To resolve its current underlying economic problems, Turkey should actually be looking to its recent past and aiming to emulate the approach pursued by former prime minister Bülent Ecevit during the 2001 financial crisis when he recruited Kemal Derviş, a senior World Bank official with extensive experience and international contacts in economic, financial, and monetary affairs.

As economy minister with a broad mandate to spearhead a durable economic recovery plan, Dervis established independent market regulatory agencies covering banking, telecommunications, energy, and other key sectors, and strengthened the competition authority.

He also either liquidated or merged insolvent banks, granted central bank autonomy to guarantee price stability, and ensured recruitment was based on competence, expertise, and meritocracy. Crucially, his productivity-enhancing restructuring blueprint was designed in Turkey rather than being imposed by the International Monetary Fund (IMF) or another external agency.

Ecevit also turbocharged reforms motivated in part by a desire to join the EU with constitutional, political and legal modernization which widened personal freedom, significantly curtailed capital punishment, liberalized the cultural environment for Kurds, and fortified the rule of law. And one of his coalition partners in that work, the right-wing pro-Turkish National Action Party (MHP), is now allied with the current ruling Justice and Development Party (AKP).

His foreign minister Ismail Cem also enhanced Turkey’s relations with both Europe and the US, initiated the so-called ‘earthquake diplomacy’ with his Greek counterpart George Papandreou after twin tragedies struck both nations in 1999, and largely avoided entanglement in Middle Eastern conflicts.

The net result of all these actions was that Turkey emerged from the crisis with greater resilience, a more robust regulatory framework, upgraded political and economic institutions, rapidly decreasing inflation, a credible central bank, a stronger financial system, closer relations with the EU and US, and heightened domestic and foreign investor confidence.

But now that similar woes are engulfing Turkey anew, is Erdogan and the AKP/MHP alliance able – and willing – to repeat the Ecevit recipe? Present signs indicate they are highly unlikely to as they are too committed to entrenching the Triple C model.

Although this model will likely further consolidate their power, it will also empty the civil service of qualified professionals, restrict civil liberties and freedoms, and create more ideological politics, affecting Turkey’s foreign policy.

Such a stubborn refusal to shift direction is increasing the inevitability of a deep economic and financial breakdown and so, unless Turkey undertakes a serious policy departure instead of continuing to resort to the quick fix approach, there is real likelihood it will simply accelerate towards disaster.

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CAMBRIDGE, England, Oct. 15, 2024 — Nu Quantum has announced a proof-of-principle prototype that advances the development of modular, distributed quantum computers by enabling connections across different qubit modalities and […]

The post Nu Quantum Unveils Qubit-Photon Interface to Enable Distributed Quantum Computing Networks appeared first on HPCwire.

SAN JOSE, Calif., Oct. 16, 2024 — Supermicro, Inc. is launching a new optimized storage system for high performance AI training, inference and HPC workloads. This JBOF (Just a Bunch […]

The post Supermicro Introduces JBOF Storage Platform Powered by NVIDIA BlueField-3 for Scalable AI and HPC appeared first on HPCwire.

CHANDLER, Ariz., Oct. 23, 2024 — The global edge computing market is expected to grow by more than 30 percent in the next five years, serving mission-critical applications in the […]

The post Microchip Expands 64-Bit Portfolio with High-Performance PIC64HX Microprocessors for Edge Computing appeared first on HPCwire.

HANOVER, Md., Nov. 5, 2024 — Ciena has announced that its optical and routing and switching innovations will once again support the SCinet network at SC24, taking place November 17–22 […]

The post Ciena Powers SC24’s SCinet with High-Speed Connectivity and Advanced Optical Solutions appeared first on HPCwire.