Robin Peter
A5005387472- Radiopharmaceutical Chemistry and Applications
- Prostate Cancer Treatment and Research
- Mass Spectrometry Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Medical Imaging Techniques and Applications
- Bladder and Urothelial Cancer Treatments
- Medical Imaging and Pathology Studies
- Radiation Therapy and Dosimetry
- Advanced Radiotherapy Techniques
- Nuclear Physics and Applications
- Effects of Radiation Exposure
- Peptidase Inhibition and Analysis
- Radioactive Decay and Measurement Techniques
- Atomic and Subatomic Physics Research
University of California, Berkeley
2022-2025
University of California, San Francisco
2022-2024
Radiopharmaceutical therapy is changing the standard of care in prostate cancer and other malignancies. We previously reported high CD46 expression 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 [225Ac]DOTA-YS5, radioimmunotherapy antibody.
Abstract Purpose: Metastatic castration-resistant prostate cancer (mCRPC) has limited treatment options and a poor prognosis. Recently, PSMA-targeted alpha particle therapy agents using Actinium-225 (225Ac) have shown promising results for treatment, but significant fraction of patients with advanced mCRPC demonstrate loss PSMA expression. We previously reported that PSMA-null PSMA-positive tumors can be detected treated effectively CD46-targeted radiopharmaceuticals. This study evaluates...
Abstract Targeted radiopharmaceutical therapy with alpha-particle emitters (αRPT) is advantageous in cancer treatment because the short range and high local energy deposition of alpha particles enable precise radiation delivery efficient tumor cell killing. However, these properties create sub-organ dose effects that are not easily characterized by direct gamma-ray imaging (PET or SPECT). We present a computational procedure to determine spatial distribution absorbed from alpha-emitting...
Radiopharmaceutical therapy using
We present a new method to measure sub-microcurie activities of photon-emitting radionuclides in organs and lesions small animals vivo. Our technique, named the collimator-less likelihood fit, combines very high sensitivity collimatorless detector with Monte Carlo-based fit order estimate previously segmented regions interest along their uncertainties. This is done directly from photon projections our region segmentation provided by an x-ray computed tomography scan. have extensively...
<p>Figure S7: Analysis of CD46 expression in correlation with the [225Ac]DOTA-YS5 uptake and DNA damage. Digital autographs, H &E staining, immunofluorescence (Rabbit Isotype control+DAPI, & phospho-γ-H2Ax) tumor tissues injected for day 1, 2, 4, 7.</p>
<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:...
<p>Figure S8: Acute toxicity study of the [225Ac]DOTA-YS5 in nude mice (n=5). A The body weights injected with showed no significant change treatment groups over 15 days period. B&C: Liver and kidney function tests (B) blood parameters (C) show changes for saline vs. treated indicating short-term safety [225Ac]DOTA-YS5.</p>
<p>Figure S11: Antitumor activity of [225Ac]DOTA-YS5 in subcutaneous DU145 tumors nude mice. Tumor volume, survival analysis, and weight measurements after the injections xenografts (n=6).</p>
<p>Figure S3: Binding of [225Ac]DOTA-YS5 to 22Rv1 with or without cold antibody blocking. Blocking YS5 results in a reduction binding from 19.25±0.70% 4.46±0.17% (n=3).</p>
<p>Figure S5: Estimated equivalent doses (in Sv) in organs and tumor indicating the highest dose (37 was delivered to tissue.</p>
<p>Figure S6: Number of H2AX-foci after the treatment saline and [225Ac]DOTA-YS5 for 7 days 14 (n=3). t-test p value is indicated as * p<0.05.</p>
<p>Figure S10: Tumor volumes, overall survival, and body weights for the saline fractionated dose (0.125 µCi x 3) injections in 22Rv1 xenografts. Results show delayed tumor growth improved survival without significant toxicity from treatment (n=10).</p>
<p>Figure S4: Gamma energy spectra of the tumor, blood, kidneys, and bone showing intensities 213Bi 221Fr peaks. As compared to equilibrium gamma [225Ac]DOTA-YS5, increased intensity was observed in kidney samples.</p>
<p>Figure S9: Histology evaluation of the healthy tissues for long-term (117 days) toxicity analysis. Hematoxylin and Eosin (H&E) staining spleen, liver, lungs, heart, bone samples show no at 0.25 µCi or 0.5 doses [225Ac]DOTA-YS5. Scale bar: 20 µm</p>
<p>Supplementary Data: Methods and tables.</p>
<p>Figure S1: Immunohistochemical staining for PSMA expression on tissue section from patient-derived xenografts. Scale bar = 200 µm</p>
<p>Figure S2: A, MALDI-TOF Mass spectroscopy results show 8.7 equivalents of DOTA molecules on the YS5 antibody. The number were calculated by dividing difference m/z between and DOTA-YS5 molecular weight DOTA. B, Size-exclusion chromatogram shows no aggregation [225Ac]DOTA-YS5 after radiolabeling steps. C, Stability tested in saline human serum for 14 days. D, Comparison binding assay attaining secular equilibrium vs without equilibrium. No significant was observed these two assays...
<p>Figure S6: Number of H2AX-foci after the treatment saline and [225Ac]DOTA-YS5 for 7 days 14 (n=3). t-test p value is indicated as * p<0.05.</p>
<p>Supplementary Data: Methods and tables.</p>
<p>Figure S8: Acute toxicity study of the [225Ac]DOTA-YS5 in nude mice (n=5). A The body weights injected with showed no significant change treatment groups over 15 days period. B&C: Liver and kidney function tests (B) blood parameters (C) show changes for saline vs. treated indicating short-term safety [225Ac]DOTA-YS5.</p>
<p>Figure S7: Analysis of CD46 expression in correlation with the [225Ac]DOTA-YS5 uptake and DNA damage. Digital autographs, H &E staining, immunofluorescence (Rabbit Isotype control+DAPI, & phospho-γ-H2Ax) tumor tissues injected for day 1, 2, 4, 7.</p>
<p>Figure S9: Histology evaluation of the healthy tissues for long-term (117 days) toxicity analysis. Hematoxylin and Eosin (H&E) staining spleen, liver, lungs, heart, bone samples show no at 0.25 µCi or 0.5 doses [225Ac]DOTA-YS5. Scale bar: 20 µm</p>
<p>Figure S11: Antitumor activity of [225Ac]DOTA-YS5 in subcutaneous DU145 tumors nude mice. Tumor volume, survival analysis, and weight measurements after the injections xenografts (n=6).</p>
<p>Figure S10: Tumor volumes, overall survival, and body weights for the saline fractionated dose (0.125 µCi x 3) injections in 22Rv1 xenografts. Results show delayed tumor growth improved survival without significant toxicity from treatment (n=10).</p>