Biology subjects

Bidkar, A. P.

Publications and source records attributed to Bidkar, A. P..

3 recordsLinked to original sources

bioRxiv2026

In vivo Quantitative Tomography of 225Ac Daughters in a Prostate Cancer Mouse Model with a Compton Camera

Targeted alpha therapy with 225Ac is a promising modality for cancer treatment, as shown in recent preclinical and clinical studies. Preclinical imaging of 225Ac is essential to fully understand the biokinetics of developmental 225Ac radiopharmaceuticals. Although single photon emission computed tomography (SPECT) is typically used to achieve this in vivo, conventional preclinical scanners struggle to provide high contrast and accurate quantification for 225Ac imaging due to the very low injected activities (below 1 kBq/g), the unfavorable gamma-ray branching ratios (<26%), and its complex decay chain with several gamma-ray emissions. In this work, we employ a compact CZT-based Compton camera to achieve quantitative tomography of 225Ac daughters in live mice at 18.5 kBq (0.5 Ci) injected activities. Three mice bearing 22Rv1 prostate cancer subcutaneous xenografts were scanned in a single bed position for 30 minutes following intravenous administration of 18.5 kBq of the Anti-CD46 225Ac-Macropa-PEG4-YS5 conjugate. We successfully visualized the in vivo biodistributions of the 225Ac daughters 221Fr and 213Bi, distinguishing between the tumor xenograft and the central organs. Quantification of the tumor uptake from the images revealed an activity as low as 1.1 kBq. In vivo activity quantification computed from the images was compared to ex vivo biodistribution measurements using a gamma counter after harvesting the tissue, showing strong agreement.

bioengineering↗

bioRxiv2025

Effective imaging and treatment of Acute Myeloid Leukemia with radiotheranostics targeting the activated conformation of integrin-Beta2

There remains an unmet clinical need for improved treatment strategies in Acute Myeloid Leukemia (AML). Although radiopharmaceutical therapies targeting non-cancer-selective antigens have shown promise in AML, their clinical utility is often limited by prolonged bone marrow suppression. Using a unique proteomics-based strategy, we recently identified the active conformation of integrin-{beta}2 (aITGB2) as a novel, tumor-selective target for AML. Importantly, this conformational epitope is expressed widely on AML cells but minimally on normal marrow progenitors/healthy tissues. Here we first confirmed widespread aITGB2 expression on AML tumors that was largely independent of tumor genotype or prior therapeutic regimen. We developed diagnostic and therapeutic radiopharmaceuticals targeting aITGB2 utilizing a conformation-specific antibody (clone 7065). PET/CT imaging with 89Zr and 134Ce-labeled 7065 in AML models revealed high target-mediated uptake, greater than that compared to standard of care [18F]-FDG. PET/CT imaging with [89Zr]DFO*-7065 showed reduced binding to normal bone marrow and immune cells in humanized immune system mice compared to [89Zr]DFO*-anti-CD33. For therapy, we developed [225Ac]Macropa-PEG4-7065 using an optimized chelator-linker combination. Treatment with [225Ac]Macropa-PEG4-7065 in Nomo-1 and PDX AML disseminated models delayed tumor growth and improved overall survival compared to controls, including [225Ac]DOTA-anti-CD33, a clinical stage-radioimmunotherapy under evaluation in AML. Relapsed tumors demonstrated persistent aITGB2 expression, supporting continued development of fractionated dosing schemes, and proteomics analysis indicated activation of TCA cycle and carbon metabolism pathways, consistent with therapy-induced stress responses. These findings highlight [89Zr]DFO*-7065 and [225Ac]Macropa-7065 as a promising aITGB2-targeted theranostic pair with potential for imaging and treatment in future clinical translation. One Sentence SummaryThis study demonstrates promising preclinical efficacy of aITGB2-targeted radiotheranostics for selective imaging and therapy in AML.

cancer biology↗

bioRxiv2022

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

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 isotope 213Bi. 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.

cancer biology↗