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

Enhancing the therapeutic index of [211At]YF2 with iodo pseudo carrier: A simple strategy for reducing accumulation in kidneys, salivary and lacrimal glands.

Journal Article Nucl Med Biol · May 11, 2025 INTRODUCTION: Low-molecular-weight (LMW) PSMA-targeted agents have enjoyed success; however, their off-target toxicity in normal tissues such as kidneys, salivary gland and lacrimal gland can be dose limiting. Herein, we have evaluated the effect of co-adm ... Full text Link to item Cite

A third generation PSMA-targeted agent [211At]YF2: Synthesis and in vivo evaluation.

Journal Article Nucl Med Biol · 2024 INTRODUCTION: Targeted α-particle therapy agents have shown promising responses in patients who have developed resistance to β--particle emitting radionuclides, albeit off-target toxicity remains a concern. Astatine-211 emits only one α-particle per decay ... Full text Link to item Cite

PSMA-reactive NB7 single domain antibody fragment: A potential scaffold for developing prostate cancer theranostics.

Journal Article Nucl Med Biol · 2024 INTRODUCTION: Single domain antibody fragments (sdAbs) are an appealing scaffold for radiopharmaceutical development due to their small size (~15 kDa), high solubility, high stability, and excellent tumor penetration. Previously, we developed NB7 sdAb, whi ... Full text Link to item Cite

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Recent Grants

Small Molecule PSMA-Targeted Alpha Therapy

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

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

ResearchCo Investigator · Awarded by Prostate Cancer Foundation · 2023 - 2025

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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