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.

Purpose: Radiopharmaceutical therapy is changing the standard of care in prostate cancer (PCa) and other malignancies. We previously reported high CD46 expression in PCa 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) PCa 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 h, 96 h, 168 h, and 408 h, respectively), compared to the healthy organs. [225Ac]DOTA-YS5 suppressed tumor size and prolonged survival in cell line 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 PSMA-positive and 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 PCa.

Radiopharmaceutical therapy is changing the standard of care in prostate cancer (PCa) and other malignancies. We previously reported high CD46 expression in PCa 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. Our radiolabeled antibody retains binding efficacy and shows a high tumor to background ratio in PCa xenografts. Furthermore, we show that radiolabeled antibody was able to suppress the growth of cell-derived and patient-derived xenografts, including PSMA-positive and deficient models. Nephrotoxicity, not seen at low radioactive doses, is evident at higher radioactivity dose levels, likely due to redistribution of daughter isotope213Bi. 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 PCa.

<p>Figure S2: A, MALDI-TOF Mass spectroscopy results show 8.7 equivalents of DOTA molecules on the YS5 antibody. The number of DOTA were calculated by dividing the difference of m/z between YS5 and DOTA-YS5 by the molecular weight of DOTA. B, Size-exclusion chromatogram shows no aggregation of the [225Ac]DOTA-YS5 after the radiolabeling steps. C, Stability of the [225Ac]DOTA-YS5 tested in saline and human serum for 14 days. D, Comparison of the binding assay results after attaining secular equilibrium vs without secular equilibrium. No significant difference was observed for these two assays (n=4). (Data represented as Mean ± SD).</p>

<p>Figure S11: Antitumor activity of [225Ac]DOTA-YS5 in subcutaneous DU145 tumors in nude mice. Tumor volume, survival analysis, and weight measurements after the injections of [225Ac]DOTA-YS5 in DU145 xenografts (n=6).</p>