Michael Rod Zalutsky

The overall objective of our laboratory is the development of novel radioactive compounds for improving the diagnosis and treatment of cancer. This work primarily involves radiohalo-genation of biomolecules via site-specific approaches, generally via demetallation reactions. Radionuclides utilized for imaging include I-123, I-124 and F-18, the later two being of particular interest because they can be used for the quantification of biochemical and physiological processes in the living human through positron emission tomography. For therapy, astatine-211 decays by the emission of alpha-particles, a type of radiation considerably more cytotoxic that the beta-particles used in conventional endoradiotherapy. The range of At-211 alpha particles is only a few cell diameters, offering the possibility of extremely focal irradiation of malignant cells while leaving neighboring cells intact. Highlights of recent work include: a)
development of reagents for protein and peptide radioiodination that decrease deiodination in vivo by up to 100-fold, b) demonstration that At-211 labeled monoclonal antibodies are effective in the treatment of a rat model of neoplastic meningitis, c) synthesis of a thymidine analogue labeled with At-211 and the demonstration that this molecule is taken up in cellular DNA with highly cytotoxicity even at levels of only one atom bound per cell and d) development of
radiohalobenzylguanidines which are specifically cytotoxic for human neuroblastoma cells.

Current Appointments & Affiliations

Jonathan Spicehandler, M.D. Distinguished Professor of Neuro Oncology, in the School of Medicine · 2008 - Present Radiology, Clinical Science Departments

Professor of Radiology · 2018 - Present Radiology, Clinical Science Departments

Professor of Radiation Oncology · 2009 - Present Radiation Oncology, Clinical Science Departments

Professor in Pathology · 2017 - Present Pathology, Clinical Science Departments

Professor of Biomedical Engineering · 2024 - Present Biomedical Engineering, Pratt School of Engineering

Member of the Duke Cancer Institute · 1985 - Present Duke Cancer Institute, Institutes and Centers

Recent Publications

Effective treatment of human prostate carcinoma xenografts with Single-Dose PSMA-targeted [211At]YF2.

Journal Article Eur J Nucl Med Mol Imaging · October 30, 2025 PURPOSE: [211At]YF2 exhibits high cytotoxicity in vitro and prolonged retention in prostate-specific membrane antigen (PSMA) expressing xenografts. Herein we evaluated its therapeutic efficacy in athymic mice with PSMA + PC3 xenografts. METHODS: The antitu ... Full text Link to item Cite

Longitudinal Imaging Reveals Tumor Uptake and Prolonged Retention of Bispecific T Cell-Engaging Antibody in GBM via Passive and Active Mechanisms.

Journal Article Clin Cancer Res · August 14, 2025 PURPOSE: This study aimed to assess the dynamics of tumor-specific uptake, retention, and blood-tumor barrier penetration of our unique IL-13 receptor α-2 × CD3 bispecific T-cell engager (BTE) following systemic administration in mice with intracranial gli ... Full text Link to item Cite

Structural analysis of nanobody interactions with their prostate-specific membrane antigen binding epitopes.

Journal Article Int J Biol Macromol · August 2025 Prostate-specific membrane antigen (PSMA), overexpressed in prostate cancer, is a promising target for diagnostics and therapy. However, the monoclonal antibodies in current use for PSMA targeting and inhibition have suboptimal activities due to their poor ... Full text Link to item Cite

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Recent Grants

Targeting neuroendocrine cells in prostate cancer with small molecule and targeted radionuclide therapies

ResearchCo Investigator · Awarded by Prostate Cancer Foundation · 2023 - 2026

Small Molecule PSMA-Targeted Alpha Therapy

ResearchPrincipal Investigator · Awarded by University of Texas Southwestern Medical Center · 2024 - 2026

PSMAi-PARPi combination agents for the targeted Auger and alpha therapy of metastatic castration-resistant prostate cancer

ResearchCo Investigator · Awarded by National Institutes of Health · 2022 - 2025

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Education, Training & Certifications

Washington University in St. Louis · 1974 Ph.D.

Washington University in St. Louis · 1972 M.A.

External Links

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