Robin Peter

University of California, Berkeley

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Youngho Seo

University of California, San Francisco

Kondapa Naidu Bobba

University of California, San Francisco

Robert R. Flavell

University of California, San Francisco

Anil P. Bidkar

Indian Institute of Technology Guwahati

Niranjan Meher

Indian Institute of Technology Guwahati

Bin Liu

University of California, San Francisco

Anju Wadhwa

University of California, San Francisco

Jiang He

Xinjiang Institute of Materia Medica

Chandrashekhar Dasari

University of California, San Francisco

Rahul Aggarwal

UCSF Helen Diller Family Comprehensive Cancer Center

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University of California, San Francisco

UCSF Helen Diller Family Comprehensive Cancer Center

University of California System

University of California, Berkeley

Fred Hutch Cancer Center

University of Washington

Berry (United States)

Cancer Research Center

Lawrence Berkeley National Laboratory

Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa

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Figure S2 from Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy

Anil P. Bidkar Sinan Wang Kondapa Naidu Bobba Emily Chan Scott Bidlingmaier

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).

DOTA

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10.1158/1078-0432.22820108

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

Anil P. Bidkar Sinan Wang Kondapa Naidu Bobba Emily Chan Scott Bidlingmaier

<div>AbstractPurpose: 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.</div>

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10.1158/1078-0432.c.6571946

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3D small-scale dosimetry and tumor control of 225Ac radiopharmaceuticals for prostate cancer

Scientific Reports (2024)

Robin Peter Anil P. Bidkar Kondapa Naidu Bobba Luann Zerefa Chandrashekhar Dasari

Radiopharmaceutical therapy using

10.1038/s41598-024-70417-3

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Treatment of prostate cancer with CD46 targeted²²⁵Ac alpha particle radioimmunotherapy

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Anil P. Bidkar Sinan Wang Kondapa Naidu Bobba Emily Chan Scott Bidlingmaier

Abstract 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 [ 225 Ac]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 isotope 213 Bi. Overall, this preclinical study confirms that [ 225 Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46 targeted radioligand therapy in PCa.

10.1101/2022.10.13.512165

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Figure S6 from Treatment of prostate cancer with CD46 targeted 225Ac alpha particle radioimmunotherapy

Anil P. Bidkar Sinan Wang Kondapa Naidu Bobba Emily Chan Scott Bidlingmaier

Figure S6: Number of H2AX-foci after the treatment of saline and [225Ac]DOTA-YS5 for 7 days and 14 days (n=3). t-test p value is indicated as * p<0.05.

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10.1158/1078-0432.27030391

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Comparison and calibration of dose delivered by ¹³⁷Cs and x-ray irradiators in mice

Physics in Medicine and Biology (2022)

J. Caravaca Rodríguez Robin Peter Jaewon Yang Chad Gunther Juan A. Cámara

The Office of Radiological Security, U.S. Department of Energy's National Nuclear Security Administration, is implementing a radiological risk reduction program which seeks to minimize or eliminate the use of high activity radiological sources, including

10.1088/1361-6560/ac9e88

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Figure S10 from Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy

Anil P. Bidkar Sinan Wang Kondapa Naidu Bobba Emily Chan Scott Bidlingmaier

Figure S10: Tumor volumes, overall survival, and body weights for the saline and fractionated dose (0.125 µCi x 3) injections in 22Rv1 xenografts. Results show delayed tumor growth and improved survival without the significant toxicity from fractionated dose treatment (n=10).

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10.1158/1078-0432.22820114

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Figure S7 from Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy

Anil P. Bidkar Sinan Wang Kondapa Naidu Bobba Emily Chan Scott Bidlingmaier

Figure S7: Analysis of CD46 expression in correlation with of the [225Ac]DOTA-YS5 uptake and DNA damage. Digital autographs, H &E staining, and immunofluorescence (Rabbit Isotype control+DAPI, CD46 & phospho-γ-H2Ax) of the tumor tissues injected with [225Ac]DOTA-YS5 for day 1, day 2, day 4, and day 7.

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10.1158/1078-0432.22820093

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Supplementary Data 1 from Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy

Anil P. Bidkar Sinan Wang Kondapa Naidu Bobba Emily Chan Scott Bidlingmaier

Supplementary Data: Methods and tables.

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10.1158/1078-0432.22820081

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Figure S8 from Treatment of Prostate Cancer with CD46-targeted 225Ac Alpha Particle Radioimmunotherapy

Anil P. Bidkar Sinan Wang Kondapa Naidu Bobba Emily Chan Scott Bidlingmaier

Figure S8: Acute toxicity study of the [225Ac]DOTA-YS5 in nude mice (n=5). A The body weights of mice injected with [225Ac]DOTA-YS5 showed no significant change in treatment groups over the 15 days study period. B&C: Liver and kidney function tests (B) and blood parameters (C) show no significant changes for saline vs. treated groups indicating the short-term safety of [225Ac]DOTA-YS5.

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Liver function

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10.1158/1078-0432.22820090.v1

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