No abstract

The past five years have seen an increasing acceptance of peptide-based prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) agents for treatment of metastatic castration-resistant prostate cancer (mCRPC), with [177Lu]-DKFZ-PSMA-617 ([177Lu]-PSMA-617) emerging as the leading candidate. [177Lu]-PSMA-617 and other PSMA ligands have shown efficacy in reducing the tumor burden in mCRPC patients but irradiation to salivary gland and kidneys is a concern and dose limiting factor. Therefore, methods to reduce non-target organ toxicity are needed to safely treat patients and preserve their quality of life. Here, we report the effects of the addition of the cold PSMA ligand DKFZ-PSMA-11 (PSMA-11) on the uptake of [177Lu]-PSMA-617 in tumor, salivary glands and kidneys. Groups of athymic nude mice (n = 4) bearing PC3-PIP (PSMA+) tumor xenografts were administered with [177Lu]-PSMA-617 along with 0, 5, 100, 500, 1000 and 2000 pmoles of PSMA-11. Biodistribution studies 1 h post-administration revealed that [177Lu]-PSMA-617 uptake in PSMA-expressing PC3-PIP tumors was 21.71±6.13, 18.7±2.03, 26.44±2.94, 16.21±3.5, 13.52±3.68, and 12.03±1.96 %ID/g when 0, 5, 100, 500, 1000 and 2000 pmoles of PSMA-11 were added, respectively. Corresponding kidney uptake values were 123.14±52.52, 132.31±47.4, 84.29±78.25, 2.12±1.88, 1.16±0.36, 0.64±0.23 %ID/g, respectively. Corresponding salivary gland uptake values were 0.48±0.11, 0.45±0.15, 0.38±0.3, 0.08±0.03, 0.09±0.07, 0.05±0.02 % ID/g, respectively. Thus, uptake of PSMA TRT agents in salivary gland and kidney can be substantially reduced without impact on tumor uptake by adding cold PSMA-11. Our data provides proof-of-concept and we propose that similar strategy be pursued in future clinical trials to prevent xerostomia and renal toxicity arising from [177Lu]-PSMA-617.

Objective: The objectives of this study were two-fold: 1) to engage community stake­holders in identifying the top three social determinant of health (SDOH) barriers to the early detection and treatment of cancer in their respective communities; and 2) to develop a tailored plan responsive to the potential social risks identified within the catchment of an urban academic cancer center.Methods: Stakeholders from four neighbor­hoods in Brooklyn, New York with dispro­portionate cancer burden were recruited; the nominal group technique, a semi-quantitative research method, was used to elicit the SDOH barriers. Responses were consolidated into categories and ranked by points received.Results: 112 stakeholders participated in four community-based meetings. The SDOH categories of economic stability, education, and community and social context were identified as the top barriers. The themes of lost wages/employment, competing priorities, and the inability to afford care embodied the responses about economic stability. The domain of education was best described by the themes of low health literacy, targeted health topics to fill gaps in knowledge, and recommendations on the best modalities for improving health knowledge. Lastly, within the category of community and social context, the themes of stigma, bias, and discrimination, eroding support systems, and cultural misconcep­tions were described.Conclusion: The implications of our study are three-fold. First, they highlight the strengths of the nominal group technique as a methodology for engaging community stakeholders. Second, our analysis led to identifying a smaller set of social priorities for which tailored screening and practical solutions could be implemented within our health care system. Third, the results provide insight into the actual types of interventions and resources that commu­nities expect from the health care sector.Ethn Dis. 2021;31(1):23-30; doi:10.18865/ ed.31.1.23