Data from Treatment of prostate cancer with CD46 targeted ²²⁵Ac alpha particle radioimmunotherapy

• DOI: 10.1158/1078-0432.c.6571946.v3
• Publication Date: 2024-09-16T11:43:18Z
• Authors: Anil P. Bidkar; Sinan Wang; Kondapa Naidu. Bobba; Emily Chan; Scott Bidlingmaier; Emily A. Egusa; Robin Peter; Umama Ali; Niranjan Meher; Anju Wadhwa; Suchi Dhrona; Chandrashekhar Da...; Denis Beckford-Vera; Yang Su; Ryan Tang; Li Zhang; Jiang He; David M. Wilson; Rahul Aggarwal; Henry F. VanBrocklin; Youngho Seo; Jonathan Chou; Bin Liu; Robert R. Flavell
• Keywords: Alpha (finance); Alpha particle

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