(University of Johannesburg) Fly ash generated by coal-fired power stations is a global environmental headache, creating groundwater and air pollution from vast landfills and ash dams. The waste product can be repurposed into geopolymer concrete, such as precast heat-cured structural elements for buildings. However, a critical durability problem has been low resistance to extreme alkali attack. UJ researchers found that high temperature heat-treatment at 200 degrees Celsius can halve this harmful mechanism in fly ash geopolymer concretes.

(US Department of Agriculture - Agricultural Research Service) A new freeze-resistant Trichinella species has been discovered in wolverines by Agricultural Research Service scientists and their colleagues. Trichinella are parasites that cause the disease trichinosis (formally referred to as trichinellosis), which people can get by eating raw or undercooked meat from infected animals.

(Queensland University of Technology) Robots that fly, swim and drive are being designed and built by internationally renowned Australian scientists from QUT.

Restaurant workers in a reopened Dallas eatery say they are being asked to weigh their safety against their jobs.

(École de technologie supérieure) The first ever standard for real-time calculation of pollutant emissions allocated to the use of information and communication technologies (ICT) was recently introduced, thanks to the work of the IEEE ICT Emissions Working Group Committe, chaired by Mohamed Cheriet, a Professor in the Systems Engineering Department at École de technologie supérieure. Under the auspices of the IEEE Standards Association, the Working Group Committee is made up of researchers from diverse backgrounds and many different countries.

(Damon Runyon Cancer Research Foundation) The first class of Damon Runyon Quantitative Biology Fellowship Awardees launched their research in novel directions that may lead to the next breakthroughs in cancer research. Nine brilliant young scientists will apply their quantitative skills to design innovative experiments and interpret massive data sets that may help solve important biological and clinical problems.

Current regulations do not effectively prevent potentially misleading claims, says Imperial scientists

(University of Oklahoma) OU Medicine recently received a $1.4 million grant from the National Institutes of Health to study one method of embryo transfer involved in IVF: cryopreserved (frozen) embryo transfer.

(University of Exeter) The public would comply with major changes to medical advice - but would then be less likely to follow other new guidelines in the future, research shows.

(University of California - Santa Cruz) Restoration ecologist Karen Holl has a simple message for anyone who thinks planting 1 trillion trees will reverse the damage of climate change: 'We can't plant our way out of climate change.'

(Clemson University) While the world admires the beauty and fragrance of flowers, most of us are missing out on the extraordinary processes these seemingly delicate life forms are carrying out every moment of the day. Matthew Koski, an assistant professor at Clemson, is not only paying attention, he is advancing his research with a three-year, $455,000 grant from the NSF for a study of flower adaptations titled 'Modifying the floral microenvironment: elevational divergence in floral thermoregulatory mechanisms.'

Closing 2019, reggae star Buju Banton celebrated the inking of a partnership deal with international entertainment group Roc Nation, founded by rapper Jay-Z. The artiste is on the promotional pathway for his 2020 album, Upside Down, which will be...

David Cluet
Apr 1, 2020; 19:701-715
Technological Innovation and Resources

Xien Yu Chua
Apr 1, 2020; 19:730-743
Technological Innovation and Resources

Adriaan Sticker
Apr 22, 2020; 0:RA119.001624v1-mcp.RA119.001624
Research

Sonia Podvin
Apr 15, 2020; 0:RA120.002079v1-mcp.RA120.002079
Research

Nora Linscheid
Apr 14, 2020; 0:RA119.001878v1-mcp.RA119.001878
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Tsung-Heng Tsai
Mar 31, 2020; 0:RA119.001792v1-mcp.RA119.001792
Research

Eva Griesser
May 1, 2020; 19:839-851
Research

Nikita Prianichnikov
Mar 10, 2020; 0:TIR119.001720v1-mcp.TIR119.001720
Technological Innovation and Resources

Chia-Feng Tsai
May 1, 2020; 19:828-838
Research

24 July 2019

Cyberattacks are increasingly challenging critical national infrastructure. This paper considers the security by design approach for civil nuclear power plants and analyses areas of risk and opportunities for the nuclear industry.

7 May 2020 , Volume 96, Number 3

Sodium–glucose cotransport 2 inhibitors (SGLT2i) lower plasma glucose but stimulate endogenous glucose production (EGP). The current study examined the effect of dapagliflozin on EGP while clamping plasma glucose, insulin, and glucagon concentrations at their fasting level. Thirty-eight patients with type 2 diabetes received an 8-h measurement of EGP ([3-³H]-glucose) on three occasions. After a 3-h tracer equilibration, subjects received 1) dapagliflozin 10 mg (n = 26) or placebo (n = 12); 2) repeat EGP measurement with the plasma glucose concentration clamped at the fasting level; and 3) repeat EGP measurement with inhibition of insulin and glucagon secretion with somatostatin infusion and replacement of basal plasma insulin and glucagon concentrations. In study 1, the change in EGP (baseline to last hour of EGP measurement) in subjects receiving dapagliflozin was 22% greater (+0.66 ± 0.11 mg/kg/min, P < 0.05) than in subjects receiving placebo, and it was associated with a significant increase in plasma glucagon and a decrease in the plasma insulin concentration compared with placebo. Under glucose clamp conditions (study 2), the change in plasma insulin and glucagon concentrations was comparable in subjects receiving dapagliflozin and placebo, yet the difference in EGP between dapagliflozin and placebo persisted (+0.71 ± 0.13 mg/kg/min, P < 0.01). Under pancreatic clamp conditions (study 3), dapagliflozin produced an initial large decrease in EGP (8% below placebo), followed by a progressive increase in EGP that was 10.6% greater than placebo during the last hour. Collectively, these results indicate that 1) the changes in plasma insulin and glucagon concentration after SGLT2i administration are secondary to the decrease in plasma glucose concentration, and 2) the dapagliflozin-induced increase in EGP cannot be explained by the increase in plasma glucagon or decrease in plasma insulin or glucose concentrations.

¹⁸F-PI-2620 is a next generation tau positron emission tomography (PET)-tracer that has demonstrated ability to image the spatial distribution of suspected tau pathology. The objective of this study was to assess the tracer biodistribution, dosimetry and quantitative methods of ¹⁸F-PI-2620 in the human brain. Full kinetic modelling approaches to quantify tau load were investigated. Non-invasive kinetic modeling approaches and semi-quantitative methods were evaluated against the full tracer kinetics. Finally, the reproducibility of PET measurements from test and retest scans was assessed. Methods: Three healthy controls (HC) and 4 Alzheimer disease (AD) subjects underwent two dynamic PET scans including arterial sampling. Distribution volume ratio (DVR) was estimated using full tracer kinetics (2 Tissue Compartment (2TC) models, Logan Graphical Analysis (LGA)) and non-invasive kinetic models (Non-Invasive Logan Graphical Analysis (NI-LGA) and the multilinear reference tissue model (MRTM2)). Standardized uptake value ratio (SUVR) was determined at different imaging windows after injection. Correlation between DVR and SUVR, effect size (Cohen’s d) and test-retest variability (TRV) were evaluated. Additionally, 6 HC subjects received one tracer administration and underwent whole-body PET for dosimetry calculation. Organ doses and the whole-body effective dose were calculated using OLINDA 2.0. Results: Strong correlation was found across different kinetic models (R2 >0.97) and between DVR(2TC) and SUVRs between 30 to 90 min with R2>0.95. Secular equilibrium was reached around 40 min post injection (p.i.) in most regions and subjects. The TRV and effect size for the SUVR across different regions was similar at 30-60 min (TRV=3.8%, d=3.80), 45-75 min (TRV=4.3%, d=3.77) and 60-90 min (TRV=4.9%, d=3.73) and increased at later time points. Elimination was via the hepatobiliary and urinary system. The whole-body effective dose was determined to be 33.3±2.1 μSv/MBq for an adult female and 33.1±1.4 μSv/MBq for an adult male with a 1.5 hour urinary bladder voiding interval. Conclusion: ¹⁸F-PI-2620 exhibits fast kinetics, suitable dosimetry and low TRV. DVR measured using the 2TC model with arterial sampling correlated strongly with DVR measured by NI-LGA, MRTM2 and SUVR. SUVR can be used for ¹⁸F-PI-2620 PET quantification of tau deposits avoiding arterial blood sampling. Static ¹⁸F-PI-2620 PET scans between 45-75min p.i. provide excellent quantification accuracy, large effect size and low TRV.

The purpose of this study was to assess the predictive and prognostic value of interim FDG PET (iPET) in evaluating early response to immuno-chemotherapy after two cycles (PET-2) in diffuse large B-cell lymphoma (DLBCL) by applying two different methods of interpretation: the Deauville visual five-point scale (5-PS) and a change in standardised uptake value by semi-quantitative evaluation. Methods: 145 patients with newly diagnosed DLBCL underwent pre-treatment PET (PET-0) and PET-2 assessment. PET-2 was classified according to both the visual 5-PS and percentage SUV changes (SUV). Receiver operating characteristic (ROC) analysis was performed to compare the accuracy of the two methods for predicting progression-free survival (PFS). Survival estimates, based on each method separately and combined, were calculated for iPET-positive (iPET+) and iPET-negative (iPET–) groups and compared. Results: Both with visual and SUV-based evaluations significant differences were found between the PFS of iPET– and iPET+ patient groups (p<0.001). Visually the best negative (NPV) and positive predictive value (PPV) occurred when iPET was defined as positive if Deauville score 4-5 (89% and 59%, respectively). Using the 66% SUV cut-off value, reported previously, NPV and PPV were 80 and 76%, respectively. SUV at 48.9% cut-off point, reported for the first time here, produced 100% specificity along with the highest sensitivity (24%). Visual and semi-quantitative SUV<48.9% assessment of each PET-2 gave the same PET-2 classification (positive or negative) in 70% (102/145) of all patients. This combined classification delivered NPV and PPV of 89% and 100% respectively, and all iPET+ patients failed to achieve or remain in remission. Conclusion: In this large consistently treated and assessed series of DLBCL, iPET had good prognostic value interpreted either visually or semi-quantitatively. We determined that the most effective SUV cut-off was at 48.9%, and that when combined with visual 5-PS assessment, a positive PET-2 was highly predictive of treatment failure.

Objectives: Lutetium-177 (¹⁷⁷Lu)-PSMA-617 (LuPSMA) is a radioligand with high affinity for prostate specific membrane antigen (PSMA) enabling targeted beta-irradiation of prostate cancer. We have previously reported favorable activity with low toxicity in a prospective phase II trial involving 30 men with metastatic castrate-resistant prostate cancer (mCRPC). We now report their longer-term outcomes including a 20 patient extension cohort and outcomes of subsequent systemic treatments following completion of trial therapy. Methods: 50 patients with PSMA-avid mCRPC who had progressed after standard therapies received up to 4 cycles of LuPSMA every 6 weeks. Endpoints included PSA response (PCWG2), toxicity (CTCAE v4.03), imaging response, patient-reported health-related quality of life (QoL), progression-free and overall survival. We also describe, as a novel finding, outcomes of men who subsequently progressed and had further systemic therapies, including LuPSMA. Results: 75 men were screened to identify 50 patients eligible for treatment. Adverse prognostic features of the cohort included short median PSA doubling time (2.3 months) and extensive prior treatment including prior docetaxel (84%), cabazitaxel (48%), and abiraterone and/or enzalutamide (90%). The mean administered radioactivity was 7.5 GBq/cycle. PSA decline ≥ 50% was achieved in 32 of 50 patients (64%, 95% CI 50-77%), including 22 patients (44%, 95% CI 30-59%) with ≥ 80% decrease. Of 27 patients with measurable soft tissue disease, 15 (56%) achieved an objective response by RECIST 1.1. The most common toxicities attributed to LuPSMA were self-limiting G1-2 dry mouth (66%), transient G1-2 nausea (48%), G3-4 thrombocytopenia (10%) and G3 anemia (10%). Brief pain inventory severity and interference scores decreased at all time points including at the 3 month follow-up with a decrease of -1.2 (95% CI -0.5 to -1.9, P = 0.001) and 1.0 (95% CI -0.2 to -0.18, P = 0.013), respectively. At a median follow-up of 31.4 months, median OS was 13.3 months (95% CI 10.5-18.7) with a significantly longer survival of 18.4 months (95% CI 13.8-23.8) in patients achieving a PSA decline ≥ 50%. At progression following prior response, further LuPSMA was administered to 15 (30%) patients (median 2 cycles commencing 359 days from enrolment) with PSA decline ≥ 50% in 11 patients (73%). 4 of 21 patients (19%) receiving other systemic therapies upon progression experienced PSA decline ≥ 50%. There were no unexpected adverse events with LuPSMA re-treatment. Conclusion: This expanded 50 patient cohort of men with extensive prior therapy confirms our earlier report of high response rates, low toxicity and improved QoL with LuPSMA radioligand therapy. Upon progression, re-challenge LuPSMA demonstrated higher response rates than other systemic therapies.

The PET radiotracer ⁶⁸Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA-11) shows potential as an imaging biomarker for recurrent and metastatic prostate cancer. The purpose of this study was to determine repeatability of ⁶⁸Ga-PSMA-HBED-CC in a test-retest trial in subjects with metastatic prostate adenocarcinoma. Methods: Subjects with metastatic prostate cancer underwent two PET/CT scans with ⁶⁸Ga-PSMA-HBED-CC within 14 days (mean 6 ± 4 d). Lesions in bone, nodes, prostate/bed, and visceral organs as well as representative normal tissues (salivary glands and spleen) were segmented separately by two readers. Absolute and percent differences in SUV_max and SUVmean were calculated for all test-retest regions. Repeatability was assessed using percentage difference, within-subject coefficient of variation (wCV), repeatability coefficient (RC), and Bland-Altman analysis. Results: 18 subjects were evaluated, 16 of which demonstrated local or metastatic disease on ⁶⁸Ga-PSMA-HBED-CC PET/CT. A total of 136 lesions were segmented in bone (n = 99), nodes (n = 27), prostate/bed (n = 7), and viscera (n = 3). The wCV for SUV_max was 11.7% for bone lesions and 13.7% for nodes. The RC was ±32.5% SUV_max for bone lesions and ±37.9% SUV_max for nodal lesions, meaning 95% of the normal variability between two measurements will be within these numbers, so larger differences are likely attributable to true biological changes in tumor rather than normal physiologic or measurement variability. wCV in the salivary glands and spleen was 8.9% and 10.7% SUVmean, respectively. Conclusion: Repeatability measurements for PET/CT test-retest with ⁶⁸Ga-PSMA-HBED-CC show a wCV 12-14% SUV_max and RC ±33-38% SUV_max in bone and nodal lesions. These estimates are an important aspect of ⁶⁸Ga-PSMA-HBED-CC as a quantitative imaging biomarker. These estimates are similar to those reported for ¹⁸F-FDG, suggesting that ⁶⁸Ga-PSMA-HBED-CC PET/CT may be useful in monitoring response to therapy.

2-Deoxy-2-[18F]fluoro-D-glucose (2-FDG) with positron emission tomography (2-FDG-PET) is undeniably useful in the clinic, among other uses, to monitor change over time using the 2-FDG standardized uptake values (SUV) metric. This report suggests some potentially serious caveats for this and related roles for 2-FDG PET. Most critical is the assumption that there is an exact proportionality between glucose metabolism and 2-FDG metabolism, called the lumped constant, LC. This report describes that LC is not constant for a specific tissue and may be variable before and after disease treatment. The purpose of this work is not to deny the clinical value of 2-FDG PET; it is a reminder that when one extends the use of an appropriately qualified imaging method, new observations may arise and further validation would be necessary. Current understanding of glucose-based energetics in vivo is based on the quantification of glucose metabolic rates with 2-FDG PET, a method that permits the non-invasive assessment in various human disorders. However, 2-FDG is only a good substrate for facilitated-glucose transporters (GLUTs) but not for sodium-dependent glucose co-transporters (SGLTs), which have recently been shown to be distributed in multiple human tissues. Thus, the GLUT-mediated in vivo glucose utilization measured by 2-FDG PET would be blinded to the potentially substantial role of functional SGLTs in glucose transport and utilization. Therefore, in these circumstances the 2-FDG LC used to quantify in vivo glucose utilization should not be expected to remain constant. 2-FDG LC variations have been especially significant in tumors, particularly at different stages of cancer development, affecting the accuracy of quantitative glucose measures and potentially limiting the prognostic value of 2-FDG, as well as its accuracy in monitoring treatments. SGLT-mediated glucose transport can be estimated using α-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside (Me-4FDG). Utilizing both 2-FDG and Me-4FDG should provide a more complete picture of glucose utilization via both GLUT and SGLT transporters in health and disease stages. Given the widespread use of 2-FDG PET to infer glucose metabolism, appreciating the potential limitations of 2-FDG as a surrogate for glucose metabolic rate and the potential reasons for variability in LC is relevant. Even when the readout for the 2-FDG PET study is only an SUV parameter, variability in LC is important, particularly if it changes over the course of disease progression (e.g., an evolving tumor).

⁶⁸Ga-DOTATOC-PET/MRI (⁶⁸Gallium-DOTATOC-positron emission tomography/magnetic resonance imaging) combines the advantages of PET in the acquisition of metabolic-functional information with the high soft tissue contrast of MRI. Standardized uptake values (SUV) in tumors were suggested as a measure of somatostatin receptor expression. A challenge with receptor ligands is, that the distribution volume is confined to tissues with tracer-uptake, potentially limiting SUV quantification. In this study, different functional, three-dimensional (3D) SUV, apparent diffusion coefficient (ADC) parameters and arterial tumor enhancement were tested for the characterization of gastroendopancreatic neuroendocrine tumors (GEP-NET). Methods: For this single-center, cross-sectional study, 22 patients with 24 histologically confirmed GEP-NET lesions (15 men/7 women; median, 61 years, range, 43-81 years), who received hybrid ⁶⁸Ga-DOTA-PET/MRI examinations at 3T between January 2017 and July 2019 met eligibility criteria. SUVs, tumor-to-background ratios (TBR), the total functional tumor volume (TFTV), ADCmean and ADCmin were measured based on volumes of interest (VOI) and examined with receiver operating characteristic analysis to determine cut-off values for differentiation between low and intermediate grade GEP-NET. Spearman’s rank correlation coefficients were used to assess correlations between functional imaging parameters. Results: The ratio of PET-derived SUVmean and diffusion-weighted imaging (DWI)-derived ADCmin was introduced as a combined variable to predict tumor grade, outperforming single predictors. Based on a threshold ratio of 0.03 to be exceeded, tumors could be classified as grade 2 with a sensitivity of 86% and specificity of 100%. SUV and functional ADC values as well as arterial contrast enhancement parameters showed non-significant and mostly negligible correlations. Conclusion: As receptor density and tumor cellularity appear to be independent, potentially complementary phenomena, the combined PET/MRI ratio SUVmean/ADCmin may be used as a novel biomarker, allowing to differentiate between grade 1 and 2 GEP-NET.

Prediction of post-operative pulmonary function in lung cancer patients before tumor resection is essential for patient selection for surgery and is conventionally done with a non-imaging segment counting method (SC) or a two-dimensional planar lung perfusion scintigraphy (PS). The purpose of this study was to compare quantitative analysis of PS to single photon emission computed tomography/computed tomography (SPECT/CT) and to estimate the accuracy of SC, PS and SPECT/CT in predicting post-operative pulmonary function in patients undergoing lobectomy. Methods: Seventy-five non-small cell lung cancer (NSCLC) patients planned for lobectomy were prospectively enrolled (68% males, average age 68.1±8 years ). All patients completed pre-operative forced expiratory volume capacity (FEV1), diffusing capacity of the lung for carbon monoxide (DLCO), Tc99m-MAA lung perfusion scintigraphy with PS and SPECT/CT quantification. A subgroup of 60 patients underwent video-assisted thoracoscopic (VATS) lobectomy and measurement of post-operative FEV1 and DLCO. Relative uptake of the lung lobes estimated by PS and SPECT/CT were compared. Predicted post-operative FEV1 and DLCO were derived from SC, PS and SPECT/CT. Prediction results were compared between the different methods and the true post-operative measurements in patients who underwent lobectomy. Results: Relative uptake measurements differed significantly between PS and SPECT/CT in right lung lobes, with a mean difference of -8.2±3.8, 18.0±5.0 and -11.5±6.1 for right upper, middle and lower lobes respectively (p<0.001). The differences between the methods in the left lung lobes were minor with a mean difference of -0.4±4.4 (p>0.05) and -2.0±4.0 (p<0.001) for left upper and lower lobes respectively. No significant difference and strong correlation (R=0.6-0.76, p<0.001) were found between predicted post-operative lung function values according to SC, PS, SPECT/CT and the actual post-operative FEV1 and DLCO. Conclusion: Although lobar quantification parameters differed significantly between PS and SPECT/CT, no significant differences were found between the predicted post-operative lung function results derived from these methods and the actual post-operative results. The additional time and effort of SPECT/CT quantification may not have an added value in patient selection for surgery. SPECT/CT may be advantageous in patients planned for right lobectomies but further research is warranted.

[S-Methyl-¹¹C](±)-7-methoxy-3-(4-(4-(methylthio)phenyl)butyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol (¹¹C-NR2B-SMe) and its enantiomers were synthesized as candidates for imaging the NR2B subunit within the N-methyl-D-aspartate receptor with positron emission tomography (PET). Methods: Brains were scanned with PET for 90 min after intravenous injection of one of the candidate radioligands into rats. To detect any NR2B specific binding of radioligand in brain, various pre-blocking or displacing agents were evaluated for their impact on the PET brain imaging data. Radiometabolites from brain and other tissues were measured ex vivo and in vitro. Results: Each radioligand gave high early whole brain uptake of radioactivity, followed by a brief fast decline and then a slow final decline. ¹¹C-(S)-NR2B-SMe was studied extensively. Ex vivo measurements showed that radioactivity in rat brain at 30 min after radioligand injection was virtually unchanged radioligand. Only less lipophilic radiometabolites appeared in plasma. High-affinity NR2B ligands, Ro-25-6981, ifenprodil, and CO10124, showed increasing preblock of whole brain radioactivity retention with increasing dose (0.01 to 1.25 mg/kg, i.v.). Five 1 antagonists (FTC146, BD1407, F3, F4, and NE100) and four 1 agonists ((+)-pentazocine, (±)-PPCC, PRE-084, (+)-SKF10047) were ineffective preblocking agents, except FTC146 and F4 at high dose. Two potent 1 receptor agonists, TC1 and SA4503, showed dose-dependent preblocking effects in the presence or absence of pharmacological 1 receptor blockade with FTC146. Conclusion: ¹¹C-(S)-NR2B-SMe has adequate NR2B-specific PET signal in rat brain to warrant further evaluation in higher species. TC1 and SA4503 likely have off-target binding to NR2B in vivo.

Quantitative evaluation of radiolabeled Prostate-Specific Membrane Antigen (PSMA) PET scans may be used to monitor treatment response in patients with prostate cancer (PCa). To interpret longitudinal differences in PSMA uptake, the intrinsic variability of tracer uptake in PCa lesions needs to be defined. The aim of this study was to investigate the repeatability of quantitative ¹⁸F-DCFPyL (a second generation ¹⁸F-PSMA-ligand) PET/CT measurements in patients with PCa. Methods: Twelve patients with metastatic PCa were prospectively included, of which 2 were excluded from final analyses. Patients received two whole-body ¹⁸F-DCFPyL PET/CT scans (median dose 317 MBq; uptake time 120 min), within median 4 days (range 1-11 days). After semi-automatic (isocontour-based) tumor delineation, the following lesion-based metrics were derived: Tumor-to-Blood ratio (TBRmean, TBRpeak, and TBRmax), Standardized Uptake Value (SUVmean, SUVpeak, SUV_max, normalized to bodyweight), tumor volume, and total lesion tracer uptake (TLU). Additionally, patient-based Total Tumor Volume (sum of PSMA-positive tumor volumes; TTV) and Total Tumor Burden (sum of all lesion TLUs; TTB) were derived. Repeatability was analyzed using repeatability coefficients (RC) and intra-class correlations (ICC). Additionally, the effect of point spread function (PSF) image reconstruction on the repeatability of uptake metrics was evaluated. Results: In total, 36 ¹⁸F-DCFPyL PET positive lesions were analyzed (up to 5 lesions per patient). RCs of TBRmean, TBRpeak, and TBRmax were 31.8%, 31.7%, and 37.3%, respectively. For SUVmean, SUVpeak, SUV_max the RCs were 24.4%, 25.3% and 31.0%, respectively. All ICC were ≥0.97. Tumor volume delineations were well repeatable, with RC 28.1% for individual lesion volumes and RC 17.0% for TTV. TTB had a RC of 23.2% and 33.4%, when based on SUVmean and TBRmean, respectively. Small lesions (<4.2mL) had worse repeatability for volume measurements. The repeatability of SUVpeak, TLU, and all patient-level metrics were not affected by PSF-reconstruction. Conclusion: ¹⁸F-DCFPyL uptake measurements are well repeatable and can be used for clinical validation in future treatment response assessment studies. Patient-based TTV may be preferred for multicenter studies since its repeatability was both high and robust to different image reconstructions.

We aimed to evaluate the diagnostic performance of ¹⁸F-FDG PET/CT for the detection of post-transplantation lymphoproliferative disorder (PTLD) in a pediatric population and explore its feasibility during response assessment. Methods: This retrospective study included 28 pediatric transplant recipients who underwent a total of 32 ¹⁸F-FDG PET/CT scans due to clinical suspicion of PTLD within an 8-year period. Pathology reports and 2-year follow-up were used as reference standard. Twenty-one response assessment ¹⁸F-FDG PET/CT scans were re-evaluated according to the Lugano criteria. Results: The diagnosis of PTLD was established in 14 patients (49%). Sensitivity, specificity, positive predictive value, and negative predictive value of ¹⁸F-FDG PET/CT for the detection of PTLD in children with a clinical suspicion of this disease, was 50% (7/14), 100% (18/18), 100% (7/7), and 72% (18/25), respectively. False-negative results occurred in patients with PTLD in the Waldeyer’s ring, cervical lymph nodes or small bowel with either non-destructive or polymorphic PTLD. Two of 5 interim ¹⁸F-FDG PET/CT scans and 3 of 9 end-of-treatment ¹⁸F-FDG PET/CT scans were false-positive. Conclusion: ¹⁸F-FDG PET/CT had good specificity and positive predictive value but low to moderate sensitivity and negative predictive value for the detection of PTLD in a 28 pediatric patient cohort with a clinical suspicion of this disease. False-negative results were confirmed in the Waldeyer’s ring, cervical lymph nodes and small bowel with either non-destructive or polymorphic PTLD subtypes. ¹⁸F-FDG PET/CT appears to have a limited role in the response assessment setting of pediatric PTLD, given the observed high proportions of false-positives both at interim and end-of-treatment evaluations.

The purpose of this study was to investigate the feasibility and diagnostic efficacy of ⁶⁸Ga-PSMA positron emission tomography/computed tomography (PET/CT) combined with PET-ultrasound image-guided biopsy in the diagnosis of prostate cancer. Methods: A total of 31 patients with previously negative prostate biopsy, but persistent elevated serum prostate specific antigen (PSA), were imaged with a ⁶⁸Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT ligand prior to undergoing repeat prostate biopsy. Based on the proposed PROMISE criteria, PSMA PET/CT results were interpreted as negative (miPSMA-ES 0-1) or positive (miPSMA-ES 2-3). All patients underwent standard template systematic biopsy with up to four additional PSMA PET-ultrasound fusion image-guided biopsy cores. The sensitivity, specificity, positive and negative predictive values, and accuracy of PSMA PET/CT were determined. In addition, the correlation between miPSMA-ES and detection rate of prostate cancer was also analyzed. Univariate logistic regression models were established using PSMA PET/CT semi-quantitative analysis parameters to predict the outcome of repeat prostate biopsy. Results: The median age of patients was 65 years (range 53-81), and the median PSA level was 18.0 ng/ml (range 5.48-49.77 ng/ml). Prostate cancer was detected in 15/31 patients (48.4%) and 12/31 patients (38.7%) had clinically significant disease. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ⁶⁸Ga-PSMA PET/CT in the diagnosis of clinically significant prostate cancer were 100.0%, 68.4%, 66.7%, 100.0% and 80.6%, respectively. The detection rate of prostate cancer increased with the increase of miPSMA-ES score. The detection rate of clinically significant prostate cancer in miPSMA-ES 0-1, 2 and 3 groups were 0%, 54.5% and 85.7% respectively. Semi-quantitative analysis of ⁶⁸Ga-PSMA PET/CT images showed that predictive models based on maximum standardized uptake value (SUV_max), tumor-to-background normal prostate SUV (SUVT/BGp) and tumor-to-background normal liver SUV (SUVratio) could effectively predict clinically significant prostate cancer; area under the curves were 0.930, 0.877, and 0.956, respectively. Conclusion: This study preliminarily confirmed that ⁶⁸Ga-PSMA PET/CT imaging combined with PET-ultrasound fusion image-guided prostate biopsy can effectively detect clinically significant prostate cancer. Prebiopsy ⁶⁸Ga-PSMA PET/CT has predictive value for clinically significant cancer in the studied patient population.

The aim of this work was to quantify the uptake of [¹⁸F]BMS-986192, a PD-L1 adnectin PET tracer, in patients with non-small-cell lung cancer (NSCLC). To this end, plasma input kinetic modeling of dynamic tumor uptake data with online arterial blood sampling was performed. In addition, the accuracy of simplified uptake metrics such as standardized uptake value (SUV) was investigated. Methods: Data from a study with [¹⁸F]BMS-986192 in patients with advanced stage NSCLC eligible for nivolumab treatment were used if a dynamic scan was available and lesions were present in the field of view of the dynamic scan. After injection of [¹⁸F]BMS-986192, a 60-minutes dynamic PET-CT scan was started, followed by a 30-min whole body PET-CT scan. Continuous arterial and discrete arterial and venous blood sampling were performed to determine a plasma input function. Tumor time activity curves were fitted by several plasma input kinetic models. Simplified uptake parameters included tumor to blood ratio as well as several SUV measures. Results: Twenty two tumors in nine patients were analyzed. The arterial plasma input single-tissue reversible compartment model with fitted blood volume fraction seems to be the most preferred model as it best fitted 11 out of 18 tumor time activity curves. The distribution volume V_T ranged from 0.4 to 4.8 mL·cm-3. Similar values were obtained with an image derived input function. From the simplified measures, SUV normalized for body weight (SUV_BW) at 50 and 67 minutes post injection correlated best with V_T, with an R² > 0.9. Conclusion: A single tissue reversible model can be used for the quantification of tumor uptake of the PD-L1 PET tracer [¹⁸F]BMS-986192. SUV_BW at 60 minutes post injection, normalized for body weight, is an accurate simplified parameter for uptake assessment of baseline studies. In order to assess its predictive value for response evaluation during PD-(L)1 immune checkpoint inhibition further validation of SUV against V_T based on an image derived input function is recommended.

The accuracy of lutetium-177 (¹⁷⁷Lu) radiotracer concentration measurements using quantitative clinical software was determined by comparing in vivo results for a digital solid-state cadmium-zinc-telluride SPECT/CT (single photon emission computed tomography / x-ray computed tomography) system to in vitro sampling. First, image acquisition parameters were assessed for an International Electrotechnical Commission (IEC) body phantom emulating clinical count rates loaded with a "lung" insert and 6 hot spheres with a 12:1 target-to-background ratio of ¹⁷⁷Lu solution. Then, the data of 28 whole-body SPECT/CT scans of 7 patients who underwent ¹⁷⁷Lu prostate membrane antigen (¹⁷⁷Lu-PSMA) radioligand therapy was retrospectively analyzed. Three users analyzed SPECT/CT images for in vivo urinary bladder radiotracer uptake using quantitative software (Q.Metrix, GE Healthcare). In vitro radiopharmaceutical concentrations were calculated using urine sampling obtained immediately after each scan, scaled to standardized uptake values (SUVs). Any in vivo/in vitro identity relations were determined by linear regression (ideally slope=1, intercept=0), within a 95 % confidence interval (CI). Phantom results demonstrated lower quantitative error for acquisitions using the 113 keV ¹⁷⁷Lu energy peak rather than including the 208 keV peak, given that only low-energy collimation was available in this camera configuration. In the clinical study, 24 in vivo/in vitro pairs were eligible for further analysis, having rejected 4 as outliers (via Cook’s distance calculations). All linear regressions (R2 ≥ 0.92, P<0.0001) provided identity in vivo/in vitro relations (95 % CI), with SUV averages from all users giving a slope of 1.03±0.09, an intercept of –0.25±0.64 g/mL, and an average residual difference of 20.4 %. Acquiring with the lower energy ¹⁷⁷Lu energy peak, solid-state SPECT/CT imaging provides an accuracy to within ~20 % for in vivo urinary bladder radiotracer concentrations. This non-invasive in vivo quantitation method can potentially improve diagnosis, improve patient management and treatment response assessment, and provide data essential to ¹⁷⁷Lu dosimetry.

Background: Prostate-specific antigen (PSA) is widely used to monitor treatment response in patients with metastatic castration-resistant prostate cancer (mCRPC). However, PSA measurements are considered only after 12 wk of treatment. We aimed to evaluate the prognostic value of early PSA changes following ¹⁷⁷Lu-labelled prostate specific membrane antigen (LuPSMA) radionuclide treatment in mCRPC patients. Methods: Men who were treated under a compassionate access program with LuPSMA at our institution and had available PSA values at baseline, at 6 wk after treatment initiation were included in this retrospective analysis. Patients were assigned to three groups based on PSA changes: 1) response: ≥30% decline, 2) progression: ≥25% increase and 3) stable: <30% decline and <25% increase. The co-primary endpoints were overall survival and imaging-based progression-free survival. The secondary end points were PSA changes at 12 wk and PSA flare-up. Results: We identified 124 eligible patients with PSA values at 6 wk. A ≥30% decline in PSA at 6 wk was associated with longer overall survival (median 16.7 mo; 95%CI 14.4–19.0) compared with patients with stable PSA (median: 11.8 mo; 95%CI 8.6–15.1; P = 0.007) and progression (median: 6.5 mo; 95%CI 5.2–7.8; p<0.001). Patients with ≥30% decline in PSA at 6 wk also had a reduced risk of imaging-based progression compared with patients with stable PSA (HR: 0.60; 95%CI 0.38–0.94; P = 0.02), while patients with PSA progression had a higher risk of imaging-based progression compared with those showing stable PSA (HR: 3.18; 95%CI 1.95–5.21; p<0.001). The percentage changes of PSA at 6 wk and 12 wk were highly associated (r=0.90; p<0.001). 29 of 31 (94%) patients who experienced early PSA progression at 6 wk achieved biochemical progression at 12 wk. Overall, only 1 of 36 (3%) patients with PSA progression at 6 wk achieved any PSA decline at 12 wk (1% of the entire cohort). Limitations of the study included its retrospective nature and the single center experience. Conclusion: PSA changes at 6 wk after LuPSMA initiation are an early indicator of long-term clinical outcome. Patients progressing by PSA after 6 wk of treatment could benefit from a very early treatment switch decision. PSA flare-up during LuPSMA treatment is very uncommon. Prospective studies are now warranted to validate our findings and potentially inform clinicians earlier on the effectiveness of LuPSMA.

We reviewed ¹¹¹In-DOTA-anti-CD45 antibody (BC8) imaging and bone marrow biopsy measurements to ascertain biodistribution and biokinetics of the radiolabeled antibody and to investigate differences based on type of hematologic malignancy. Methods: Serial whole-body scintigraphic images (4 time-points) were obtained after infusion of the ¹¹¹In-DOTA-BC8 (176-406 MBq) in 52 adult patients with hematologic malignancies (lymphoma, multiple myeloma, acute myeloid leukemia and myelodysplastic syndrome). Counts were obtained for the regions of interest for spleen, liver, kidneys, testicles (in males), and two marrow sites (acetabulum and sacrum) and correction for attenuation and background was made. Bone marrow biopsies were obtained 14-24 hours post-infusion and percent of administered activity was determined. Radiation absorbed doses were calculated. Results: Initial uptake in liver averaged 32% ± 8.4% (S.D.) of administered activity (52 patients), which cleared monoexponentially with biological half-time of 293 ± 157 hours (33 patients) or did not clear (19 patients). Initial uptake in spleen averaged 22% ± 12% and cleared with a biological half-time 271 ± 185 hours (36 patients) or longer (6 patients). Initial uptake in kidney averaged 2.4% ± 2.0% and cleared with a biological half-time of 243 ± 144 hours (27 patients) or longer (9 patients). Initial uptake in red marrow averaged 23% ± 11% and cleared with half-times of 215 ± 107 hours (43 patients) or longer (5 patients). Whole-body retention half-times averaged 198 ± 75 hours. Splenic uptake was higher in the AML/MDS group when compared to the lymphoma group (p ≤ 0.05) and to the multiple myeloma group (p ≤ 0.10). Liver represented the dose-limiting organ. For liver uptake, no significant differences were observed between the three malignancy groups. Average calculated radiation absorbed doses per unit administered activity for a therapy infusions of ⁹⁰Y-DOTA-BC8 were for red marrow: 470 ± 260 cGy/MBq, liver 1100 ± 330 cGy/MBq, spleen 4120 ± 1950 cGy/MBq, total body 7520 ± 20 cGy/MBq, osteogenic cells 290 ± 200 cGy/MBq, and kidneys 240 ± 200 cGy/MBqR. Conclusion: ¹¹¹In-DOTA-BC8 had long retention time in liver, spleen, kidneys, and red marrow, and the highest absorbed doses were calculated for spleen and liver. Few differences were observed by malignancy type. The exception was greater splenic uptake among leukemia/MDS group when compared to lymphoma and multiple myeloma groups.

Introduction: Neuroendocrine differentiation is associated with treatment failure and poor outcome in metastatic castration-resistant prostate cancer (mCRPC). We investigated the effect of circulating neuroendocrine biomarkers on the efficacy of PSMA-targeted radioligand therapy (RLT). Methods: Neuroendocrine biomarker profiles (progastrin-releasing peptide, neuron-specific enolase, and chromogranin-A) were analyzed in 50 patients commencing ¹⁷⁷Lu-PSMA-617 RLT. The primary endpoint was PSA response in relation to baseline neuroendocrine marker profiles. Additional endpoints included progression-free survival. Tumor uptake on post-therapeutic scans, a known predictive marker for response, was used as control-variable. Results: Neuroendocrine biomarker profiles were abnormal in the majority of patients. Neuroendocrine biomarker levels did not predict treatment failure or early progression (P ≥ 0.13). By contrast, intense PSMA-ligand uptake in metastases predicted both treatment response (P = 0.0030) and reduced risk of early progression (P = 0.0111). Conclusion: Neuroendocrine marker profiles do not predict adverse outcome of RLT. By contrast, high ligand uptake was confirmed to be crucial for achieving tumor-response.

Cancer Survival is related to tumor volume. FDG PET measurement of tumor volume holds promise but is not yet a clinical tool. Measurements come in two forms: the total lesion volume (TLV) based on the number of voxels in the tumor and secondly the total lesion glycolysis (TLG) which is the TLV multiplied by the average SUL per voxel of the tumor (SUL is the standardize uptake value normalized for lean mass). In this study we measured tumor volume in patients with malignant pleural mesothelioma (MPM). METHODS: A threshold-based program in IDL was developed to measure tumor volume in FDG PET images. 19 patients with malignant pleural mesothelioma (MPM) were studied before and after two cycles (6 weeks) of chemo-immunotherapy. Measurements included the total lesion volume (TLV), Total Lesion Glycolysis (TLG), the sum of the SULs in the tumor (SUL- total), a measure of total FDG uptake, and the average SUL per voxel. RESULTS: Baseline MPM volumes (TLV) ranged from 11 to 2610 cc. TLG values ranged from 32 to 8552 SUL-cc and were strongly correlated with TLV. While tumor volumes ranged over 3 orders of magnitude, the average SUL per voxel, SUL-average, stayed within a narrow range of 2.4 to 5.3 units. Thus, TLV was the major component of TLG while SUL-average was a minor component and was essentially constant. Further evaluation of SUL-average showed that in this cohort it’s two components SUL-total and tumor volume changed in parallel and were strongly correlated, r= 0.99, p<.01. Thus, whether the tumors were large or small, the FDG uptake as measured by SUL-total was proportional to the total tumor volume. Conclusion: TLG equals TLV multiplied by the average SUL per voxel, essentially TLV multiplied by a constant. Thus TLG, commonly considered a measure of "metabolic activity" in tumors, is also in this cohort a measure of tumor volume. The constancy of SUL per voxel is due to FDG uptake being proportional to tumor volume. Thus, in this study, the FDG uptake was also a measure of volume.

Introduction: Gastrin Releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a ⁶⁸Ga-labelled antagonist to GRPRs, NeoBOMB1, was developed for PET. We report on the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) within the EU-FP7 project Closed-loop Molecular Environment for Minimally Invasive Treatment of Patients with Metastatic Gastrointestinal Stromal Tumours (‘MITIGATE’) (grant agreement number 602306) in patients with oligometastatic gastrointestinal stromal tumors (GIST). Materials and Methods: The main objectives were evaluation of safety, biodistribution, dosimetry and preliminary tumor targeting of ⁶⁸Ga-NeoBOMB1 in patients with advanced TKI-treated GIST using PET/CT. Six patients with histologically confirmed GIST and unresectable primary or metastases undergoing an extended protocol for detailed pharmacokinetic analysis were included. ⁶⁸Ga-NeoBOMB1 was prepared using a kit procedure with a licensed ⁶⁸Ge/⁶⁸Ga generator. 3 MBq/kg body-weight were injected intravenously and safety parameters were assessed. PET/CT included dynamic imaging at 5 min, 11 min and 19 min as well as static imaging at 1, 2 and 3-4 h p.i. for dosimetry calculations. Venous blood samples and urine were collected for pharmacokinetics. Tumor targeting was assessed on a per-lesion and per-patient basis. Results: ⁶⁸Ga-NeoBOMB1 (50 µg) was prepared with high radiochemical purity (yield >97%). Patients received 174 ± 28 MBq of the radiotracer, which was well tolerated in all patients over a follow-up period of 4 weeks. Dosimetry calculations revealed a mean adsorbed effective dose of 0.029 ± 0.06 mSv/MBq with highest organ dose to the pancreas (0.274 ± 0.099 mSv/MBq). Mean plasma half-life was 27.3 min with primarily renal clearance (mean 25.7 ± 5.4% of injected dose 4h p.i.). Plasma metabolite analyses revealed high stability, metabolites were only detected in the urine. In three patients a significant uptake with increasing maximum standard uptake values (SUV_max at 2h p.i.: 4.3 to 25.9) over time was found in tumor lesions. Conclusion: This Phase I/IIa study provides safety data for ⁶⁸Ga-NeoBOMB1, a promising radiopharmaceutical for targeting GRPR-expressing tumors. Safety profiles and pharmacokinetics are suitable for PET imaging and absorbed dose estimates are comparable to other ⁶⁸Ga-labelled radiopharmaceuticals used in clinical routine.

Prostate specific membrane antigen (PSMA) targeting Positron Emission Tomography (PET) imaging is becoming the reference standard for prostate cancer (PC) staging, especially in advanced disease. Yet, the implications of PSMA-PET derived whole-body tumor volume for overall survival are poorly elucidated to date. This might be due to the fact that (semi-) automated quantification of whole-body tumor volume as PSMA-PET biomarker is an unmet clinical challenge. Therefore, a novel semi-automated software is proposed and evaluated by the present study, which enables the semi-automated quantification of PSMA-PET biomarkers such as whole-body tumor volume. Methods: The proposed quantification is implemented as a research prototype (MI Whole Body Analysis Suite, v1.0, Siemens Medical Solutions USA, Inc., Knoxville, TN). PSMA accumulating foci were automatically segmented by a percental threshold (50% of local SUV_max). Neural networks were trained to segment organs in PET-CT acquisitions (training CTs: 8,632, validation CTs: 53). Thereby, PSMA foci within organs of physiologic PSMA uptake were semi-automatically excluded from the analysis. Pretherapeutic PSMA-PET-CTs of 40 consecutive patients treated with ¹⁷⁷Lu-PSMA-617 therapy were evaluated in this analysis. The volumetric whole-body tumor volume (PSMATV50), SUV_max, SUVmean and other whole-body imaging biomarkers were calculated for each patient. Semi-automatically derived results were compared with manual readings in a sub-cohort (by one nuclear medicine physician using syngo.MM Oncology software, Siemens Healthineers, Knoxville, TN). Additionally, an inter-observer evaluation of the semi-automated approach was performed in a sub-cohort (by two nuclear medicine physicians). Results: Manually and semi automatically derived PSMA metrics were highly correlated (PSMATV50: R2=1.000; p<0.001; SUV_max: R2=0.988; p<0.001). The inter-observer agreement of the semi-automated workflow was also high (PSMATV50: R2=1.000; p<0.001; ICC=1.000; SUV_max: R2=0.988; p<0.001; ICC=0.997). PSMATV50 [ml] was a significant predictor of overall survival (HR: 1.004; 95%CI: 1.001-1.006, P = 0.002) and remained so in a multivariate regression including other biomarkers (HR: 1.004; 95%CI: 1.001-1.006 P = 0.004). Conclusion: PSMATV50 is a promising PSMA-PET biomarker that is reproducible and easily quantified by the proposed semi-automated software. Moreover, PSMATV50 is a significant predictor of overall survival in patients with advanced prostate cancer that receive ¹⁷⁷Lu-PSMA-617 therapy.

At diagnosis 22% of colorectal cancer (CRC) patients have metastases and 50% later develop metastasis. Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (¹⁷⁷Lu)-PSMA-617 is employed to treat metastatic prostate cancer (PC). ¹⁷⁷Lu-PSMA-617 targets Prostate Specific Membrane Antigen (PSMA) a cell surface protein enriched in PC and the neovasculature of other solid tumors including CRC. We performed gallium-68 (⁶⁸Ga)-PSMA-11 PET-CT imaging of ten metastatic CRC patients to assess metastasis avidity. Eight patients had lesions lacking avidity and two had solitary metastases exhibiting very low avidity. Despite expression of PSMA in CRC neovasculature, none of the patients exhibited tumor avidity sufficient to be considered for ¹⁷⁷Lu-PSMA-617 PRRT.

Purpose: This study is designed to assess the safety and therapeutic response to ¹⁷⁷Lu-EB-PSMA treatment with escalating doses in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: With institutional review board approval and informed consent, patients were randomly divided into three groups: Group A (n = 10) were treated with 1.18 ± 0.09 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Group B (n = 10) were treated with 2.12 ± 0.19 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Group C (n = 8) were treated with 3.52 ± 0.58 GBq/dose of ¹⁷⁷Lu-EB-PSMA. Eligible patients received up to three cycles of ¹⁷⁷Lu-EB-PSMA therapy, at eight-week intervals. Results: Due to disease progression or bone marrow suppression, 4 out of 10, 5 out of 10, and 5 out of 10 patients completed three cycles therapy as planned in Groups A, B, and C, respectively. The prostate-specific antigen (PSA) response was correlated with treatment dose, with PSA disease control rates in Group B (70%) and C (75%) being higher than that in Group A (10%) (P = 0.007), but no correlation between Group B and Group C was found. ⁶⁸Ga-PSMA PET/CT showed response in all the treatment groups, however, there was no significant difference between the three groups. Hematologic toxicity study found that platelets in Group B and Group C decreased more than those in Group A, and that Grade 4 thrombocytopenia occurred in 2 (25.0%) patients in Group C. No serious nephritic or hepatic side effects were observed. Conclusion: This study demonstrates that 2.12 GBq/dose of ¹⁷⁷Lu-EB-PSMA seems to be safe and adequate in tumor treatment. Further investigations with increased number of patients are warranted.

Background: The management for totally thyroidectomized differentiated thyroid cancer (TT-DTC) patients with unexplained hyperthyroglobulinemia remains indeterminate due to evidence scarcity. This multicenter study aimed at prospectively evaluating the response to radioiodine (¹³¹I) adjuvant therapy (RAT) and its potential role in risk stratification and causal clarification. Methods: TT-DTC patients with stimulated serum thyroglobulin (Tgoff) levels > 10 ng/mL but no structurally evident disease were consecutively enrolled in five tertiary care institutions. After the administration of 5.55 GBq of ¹³¹I, the risk of presence of persistent/recurrent/metastatic DTC (prmDTC) was compared to that before RAT. The causes of hyperthyroglobulinemia were explored and the response to RAT was assessed 6-12 months post RAT. The change in suppressed thyroglobulin (Tgon) level was reported. Results: A cohort of 254 subjects with a median Tgoff of 27.1 ng/mL was enrolled for the analyses. Immediately after RAT, low-, intermediate-, and high-risk were identified in 5.9%, 88.6%, and 5.5% patients, respectively, with no significant difference in risk stratification compared with that before RAT (P = 0.952). During the follow-up (median, 10.6 months), hyperthyroglobulinemia was ultimately attributed to thyroid remnant, biochemical disease, and structural/functional disease in 17.3%, 54.3%, and 28.3% of subjects, respectively. In addition, excellent, indeterminate, biochemical incomplete, and structural/functional incomplete responses were achieved in 18.1%, 27.2%, 36.2%, and 18.5% of patients, respectively. Notably, distribution for either cause of hyperthyroglobulinemia or response to RAT was comparable among the three postoperative risk groups. Tgon levels in patients who merely received RAT declined significantly over time. Conclusion: Our study demonstrated that over 90% of TT-DTC patients with unexplained hyperthyroglobulinemia are stratified as intermediate-high risk, and RAT using 5.55 GBq of ¹³¹I reveals biochemical/functional/structural disease and yields non-structural/functional incomplete response in more than 80% patients, suggesting TT-DTC patients with unexplained hyperthyroglobulinemia as explicit candidates for RAT.

Rationale: To conduct a retrospective study comparing three ¹²³I-FP-CIT-SPECT quantitative methods in patients with neurodegenerative syndromes as referenced to neuropathological findings. Methods: ¹²³I-FP-CIT-SPECT and neuropathological findings among patients with neurodegenerative syndromes from the Mayo Alzheimer's Disease Research Center and Mayo Clinic Study of Aging were examined. Three ¹²³I-FP-CIT-SPECT quantitative assessment Methods: MIMneuro (MIM Software Inc.), DaTQUANT (GE Healthcare), and manual region of interest (ROI) creation on an Advantage Workstation (GE Healthcare) were compared to neuropathological findings describing the presence or absence of Lewy body disease (LBD). Striatum to background ratios (SBRs) generated by DaTQUANT were compared to the calculated SBRs of the manual method and MIMneuro. The left and right SBRs for caudate, putamen and striatum were evaluated with the manual method. For DaTQUANT and MIMneuro the left, right, total and average SBRs and z-scores for whole striatum, caudate, putamen, anterior putamen, and posterior putamen were calculated. Results: The cohort included 24 patients [20 (83%) male, aged 75.4 +/- 10.0 at death]. The antemortem clinical diagnoses were Alzheimer’s disease dementia (ADem, N = 6), probable dementia with Lewy bodies (pDLB, N = 12), mixed ADem/pDLB (N = 1), Parkinson’s disease with mild cognitive impairment (N = 2), corticobasal syndrome (N = 1), idiopathic rapid eye movement sleep behavior disorder (iRBD) (N = 1) and behavioral variant frontotemporal dementia (N = 1). Seventeen (71%) had LBD pathology. All three ¹²³I-FP-CIT-SPECT quantitative methods had area under the receiver operating characteristics (AUROC) values above 0.93 and up to 1.000 (p<0.001) and showed excellent discrimination between LBD and non-LBD patients in each region assessed, p<.001. There was no significant difference between the accuracy of the regions in discriminating the two groups, with good discrimination for both caudate and putamen. Conclusion: All three ¹²³I-FP-CIT-SPECT quantitative methods showed excellent discrimination between LBD and non-LBD patients in each region assessed, using both SBRs and z-scores.

Invitation Only Research Event

Event participants

Professor Nick Binedell, Founding Director and Sasol Chair of Strategic Management, Gordon Institute of Business Science (GIBS), University of Pretoria