Due to challenges in performing routine personalized dosimetry in radiopharmaceutical therapies, interest in single-time-point (STP) dosimetry, particularly utilizing only one SPECT scan, is on the rise.Meanwhile, there are questions about reliability of STP dosimetry, with limited independent validations.In the present work, we analyze two STP dosimetry methods and evaluate dose errors for a number of radiopharmaceuticals based on effective half-life distributions. Method:We first challenged the common assumption that radiopharmaceutical effective half-lives across the population are Gaussian (normal) distributed. Then, dose accuracy was estimated based on two STP dosimetry methods for a wide range of potential scan-times post-injection (p.i.), for different radiopharmaceuticals applied to neuroendocrine tumors and prostate cancer. The accuracy and limitations of using each of the STP methods were discussed.Results: Log-normal distribution was shown as more appropriate to capture effective half-life distributions. The STP framework was shown as promising for dosimetry of 177 Lu-DOTATATE, and for kidney dosimetry of different radiopharmaceuticals (errors<30%). Meanwhile, for some radiopharmaceuticals, STP accuracy is compromised (e.g. in bone marrow and tumors for 177 Lu-PSMA therapies). Optimal SPECT scanning time for 177 Lu-DOTATATE is at ~72 h p.i., while 48 h p.i. would be better for 177 Lu-PSMA compounds. Conclusion:Our results demonstrate that simplified STP dosimetry methods may compromise the accuracy of dose estimates, with some exceptions such as for 177 Lu-DOTATATE and for kidney dosimetry in different radiopharmaceuticals. Simplified personalized dosimetry in the clinic continues to be a challenging task. Based on these results, we make suggestions and recommendations for improved personalized dosimetry using simplified imaging schemes. * The data of effective half-lives were published in the format of median and range only. For Studies 3 and 9, their corresponding values of mean and SD were then calculated based on method by Hozo et al 2005 (19). For Study 4, we had access to complete listing of effective half-lives. † The 95% CI of range was estimated assuming log-normal statistics, as described in the text. ‡ T eff of each individual ROI (organ or lesion) was available (i.e. complete listing of effective half-lives for all patients). § This overall dataset (29 patients) consisted primarily of 177 Lu-DOTATATE (22 patients) but also included some 177 Lu-DOTATOC ( 7patients).

Introduction: Prostate-specific membrane antigen (PSMA) is a promising novel molecular target for imaging diagnostics and therapeutics (theranostics). There has been a growing body of evidence supporting PSMA theranostics approaches in optimizing the management of prostate cancer and potentially altering its natural history. Methods: We utilized PubMed and Google Scholar for published studies, and clinicaltrials.gov for planned, ongoing, and completed clinical trials in PSMA theranostics as of June 2021. We presented evolving evidence for various PSMA-targeted radiopharmaceutical agents in the treatment paradigm for prostate cancer, as well as combination treatment strategies with other targeted therapy and immunotherapy. We highlighted the emerging evidence of PSMA and fluorodeoxyglucose (FDG) PET/CT as a predictive biomarker for PSMA radioligand therapy. We identified seven ongoing clinical trials in oligometastatic-directed therapy using PSMA PET imaging. We also presented a schematic overview of 17 key PSMA theranostic clinical trials throughout the various stages of prostate cancer. Conclusions: In this review, we presented the contemporary and future landscape of theranostic applications in prostate cancer with a focus on PSMA ligands. As PSMA theranostics will soon become the standard of care for the management of prostate cancer, we underscore the importance of integrating nuclear medicine physicians into the multidisciplinary team.

Background PET imaging of glucose metabolism has revealed presymptomatic abnormalities in genetic FTD but has not been explored in MAPT P301L mutation carriers. This study aimed to explore the patterns of presymptomatic hypometabolism and atrophy in MAPT P301L mutation carriers. Methods Eighteen asymptomatic members from five families with a P301L MAPT mutation were recruited to the study, six mutation carriers, and twelve mutation-negative controls. All participants underwent standard behavioural and cognitive assessment as well as [18F]FDG-PET and 3D T1-weighted MRI brain scans. Regional standardised uptake value ratios (SUVR) for the PET scan and volumes calculated from an automated segmentation for the MRI were obtained and compared between the mutation carrier and control groups. Results The mean (standard deviation) estimated years from symptom onset was 12.5 (3.6) in the mutation carrier group with a range of 7 to 18 years. No differences in cognition were seen between the groups, and all mutation carriers had a global CDR plus NACC FTLD of 0. Significant reduction in [18F] FDG uptake in the anterior cingulate was seen in mutation carriers (mean 1.25 [standard deviation 0.07]) compared to controls (1.36 [0.09]). A similar significant reduction was also seen in grey matter volume in the anterior cingulate in mutation carriers (0.60% [0.06%]) compared to controls (0.68% [0.08%]). No other group differences were seen in other regions. Conclusions Anterior cingulate hypometabolism and atrophy are both apparent presymptomatically in a cohort of P301L MAPT mutation carriers. Such a specific marker may prove to be helpful in stratification of presymptomatic mutation carriers in future trials.