Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy.

PURPOSE: Radiopharmaceutical therapy is changing the standard of care in prostate cancer and other malignancies. We previously reported high CD46 expression in prostate cancer and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody. EXPERIMENTAL DESIGN: [225Ac]DOTA-YS5 was developed, and its therapeutic efficiency was tested on cell-derived (22Rv1, DU145), and patient-derived (LTL-545, LTL484) prostate cancer xenograft models. Biodistribution studies were carried out on 22Rv1 tumor xenograft models to confirm the targeting efficacy. Toxicity analysis of the [225Ac]DOTA-YS5 was carried out on nu/nu mice to study short-term (acute) and long-term (chronic) toxicity. RESULTS: Biodistribution study shows that [225Ac]DOTA-YS5 agent delivers high levels of radiation to the tumor tissue (11.64% ± 1.37%ID/g, 28.58% ± 10.88%ID/g, 29.35% ± 7.76%ID/g, and 31.78% ± 5.89%ID/g at 24, 96, 168, and 408 hours, respectively), compared with the healthy organs. [225Ac]DOTA-YS5 suppressed tumor size and prolonged survival in cell line-derived and patient-derived xenograft models. Toxicity analysis revealed that the 0.5 µCi activity levels showed toxicity to the kidneys, likely due to redistribution of daughter isotope 213Bi. CONCLUSIONS: [225Ac]DOTA-YS5 suppressed the growth of cell-derived and patient-derived xenografts, including prostate-specific membrane antigen-positive and prostate-specific membrane antigen-deficient models. Overall, this preclinical study confirms that [225Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46-targeted radioligand therapy in prostate cancer.

Health Literacy, Health Outcomes and Equity: A Trend Analysis Based on a Population Survey.

Health literacy continues to be an issue among minority groups. Population surveys are one strategy used to help better understand health disparities. The Behavioral Risk Factor Surveillance System (BRFSS) in Kansas added health literacy questions to the survey in 2012. This study examined population health literacy levels and health trends from 2012 to 2018. The health status variables included health care coverage status, general health rating, presence of chronic conditions, and length of time since the last check-up. The percentage of individuals reporting low health literacy decreased from 67% in 2012 to 51% in 2018. The percentage of participants with income levels less than $15 000 was 9% in 2012 and 7% in 2018. Health literacy was lowest among the age group 18 to 24-year-olds, those who identified as multiracial, separated, not graduated from high school, out of work for more than 1 year, income less than $10 000, with other living arrangements, and living in a suburban county of metropolitan statistical area. Additionally, many health conditions improved, and those reporting health insurance increased slightly. The study demonstrates how health literacy continues to be an issue, and how education and primary prevention are necessary to improve limited health literacy and health outcomes. Findings from both state-level and national BRFSS population surveys can help educate the public health and clinical health services workforce to provide better care and address health disparities for highrisk populations.