ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Effective Treatment of Disseminated Prostate Cancer Using CD46-Targeted 225Ac Therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Identification of hepatitis B virus-associated membrane proteins as prognostic biomarkers for hepatocellular carcinoma based on retrospective analysis of integrated membrane proteomics.Translational cancer research · 2026Article
- The Next Frontier in Quantitative Co-Clinical Imaging to Advance Functional Precision Oncology.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Progress in the application ofAnnals of nuclear medicine · 2026Review
- Detecting Bacteria in Their Mammalian Hosts Using Metabolism-Targeted [ACS central science · 2026Article
- Synergistic Treatment of Prostate Cancer and Multiple Myeloma using CD46-Targeted Radioimmunotherapy Antibody-Drug Conjugates.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Compton Imaging of Ac-225 In Pre-clinical Phantoms With a 3D-positioning CZT Camera.IEEE transactions on radiation and plasma medical sciences · 2026Article
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Authors and funding
24 authors.
Funding
Abstract
purposeMetastatic castration-resistant prostate cancer has limited treatment options and a poor prognosis. Recently, prostate-specific membrane antigen (PSMA)-targeted alpha-particle therapy agents using actinium-225 (225Ac) have shown promising results in prostate cancer treatment, but a significant fraction of patients with advanced mCRPC demonstrate loss of PSMA expression. We have previously reported that PSMA-null and PSMA-positive tumors can be detected and treated effectively with CD46-targeted radiopharmaceuticals. This study evaluates the CD46-targeting PET imaging agent [89Zr]DFO-YS5, and the radioimmunotherapy agent [225Ac]Macropa-PEG4-YS5, in disseminated prostate cancer tumors. EXPERIMENTAL
designMicrotumor lesions, primarily observed in the liver, kidneys, and lungs, were successfully detected with [89Zr]DFO-YS5 PET imaging. We used disseminated 22Rv1 tumors for biodistribution studies, dosimetry assessments, and therapeutic efficacy evaluations of [225Ac]Macropa-PEG4-YS5.
resultsQuantitative digital alpha-particle autoradiography revealed high radiation dose deposition from [225Ac]Macropa-PEG4-YS5 in microtumors compared with surrounding liver tissues, although in larger lesions (>1 mm diameter), the dose distribution was heterogeneous. Early treatment of smaller disseminated tumors with a uniform radiation dose was more effective in ablating tumors and promoting survival. In late-stage lesions of large size, heterogeneous dose deposition limited therapeutic efficacy, requiring higher administered activity to achieve a complete response.
conclusionsOur findings highlight that [225Ac]Macropa-PEG4-YS5 holds the potential for clinical translation for metastatic prostate cancer and reinforces the value of microdosimetry in understanding the efficacy of and resistance to targeted alpha therapy. See related commentary by Patel et al., p. 2847.
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