Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (α) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prostate cancer. In this comprehensive review, we discuss the current consensus regarding the properties of the α-particle-emitting radionuclides that are potentially relevant for use in the clinic; the TAT-mediated mechanisms responsible for cell death; the different classes of targeting moieties and radiometal chelators available for TAT development; current approaches to calculating radiation dosimetry for TATs; and lead optimization via medicinal chemistry to improve the TAT radiopharmaceutical properties. We have also summarized the use of TATs in pre-clinical and clinical studies to date.

The diagnostic and treatment landscapes of prostate cancer are rapidly evolving. This has led to several challenges and controversies regarding optimal management of the disease that outpace guidelines and clinical data. Multidisciplinary teams (MDTs) can be used to engage the array of specialists that collaborate to treat complex malignancies such as prostate cancer. While the rationale for the use of MDTs in prostate cancer is well known, ways to optimally use MDTs to address the challenges and controversies associated with prostate cancer management are less well understood. One area of MDT care that remains undefined is how MDTs can most effectively provide guidance on clinical decision-making in situations in which information from novel diagnostic testing (genetic testing, molecular imaging) is substantially different from the established clinical risk factors. In this review, we provide a clinical perspective on ways that MDTs can be used to address this and other challenges and controversies across the prostate cancer disease continuum, from diagnosis to end-of-life considerations. Beyond clinical scenarios, we also review ways in which MDTs can mitigate disparities of care in prostate cancer. Overall, MDTs play a central role in helping to address the daily vexing issues faced by clinicians related to diagnosis, risk stratification, and treatment. Given the accelerating advances in precision medicine and targeted therapy, and the new questions and controversies these will bring, the value of MDTs for prostate cancer management will only increase in the future.

To evaluate the value of pre-treatment 18F-FDG PET/CT in patients with HCC following liver radioembolization. We identified 34 patients with HCC who underwent an FDG PET/CT scan prior to hepatic radioembolization at our institution between 2009 and 2013. Patients were seen in clinic one month after radioembolization and then at 2-3 mo intervals. We assessed the influence of FDG tumor uptake on outcomes including local liver control (LLC), distant liver control (DLC), time to distant metastases (DM), progression free survival (PFS) and overall survival (OS). The majority of patients were males (n = 25, 74%), and had Child Pugh Class A (n = 31, 91%), with a median age of 68 years (46-84 years). FDG-avid disease was found in 19 (56%) patients with SUVmax ranging from 3 to 20. Female patients were more likely to have an FDG-avid HCC (P = 0.02). Median follow up of patients following radioembolization was 12 months (1.2-62.8 mo). FDG-avid disease was associated with a decreased 1 year LLC, DLC, DM and PFS (P < 0.05). Using multivariate analysis, FDG avidity predicted for LLC, DLC, and PFS (all P < 0.05). In this retrospective study, pre-treatment HCC FDG-avidity was found to be associated with worse LLC, DLC, and PFS following radioembolization. Larger studies are needed to validate our initial findings to assess the role of F-18-FDG PET/CT scans as biomarker for patients with HCC following radioembolization.