Jonathan Spicehandler, M.D. Distinguished Professor of Neuro Oncology, in the School of Medicine
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.
Appointments and Affiliations
- Jonathan Spicehandler, M.D. Distinguished Professor of Neuro Oncology, in the School of Medicine
- Professor of Radiology
- Professor in Pathology
- Professor of Radiation Oncology
- Member of the Duke Cancer Institute
Contact Information
- Office Location: 311 Research Drive, 161H Bryan Res Bldg, Durham, NC 27710
- Email Address: zalut001@mc.duke.edu
- Websites:
Education
- M.A. Washington University in St. Louis, 1972
- Ph.D. Washington University in St. Louis, 1974
Awards, Honors, and Distinctions
- Aebersold Award. Socienty of Nuclear Medicine. 2007
- MERIT Award. National Institutes of Health. 2005
Representative Publications
- Huynh, Truc T., Yutian Feng, Rebecca Meshaw, Xiao-Guang Zhao, Lior Rosenfeld, Ganesan Vaidyanathan, Niv Papo, and Michael R. Zalutsky. “PSMA-reactive NB7 single domain antibody fragment: A potential scaffold for developing prostate cancer theranostics.” Nucl Med Biol 134–135 (2024): 108913. https://doi.org/10.1016/j.nucmedbio.2024.108913.
- Feng, Yutian, Rebecca L. Meshaw, Sean W. Finch, Yongxiang Zheng, Il Minn, Ganesan Vaidyanathan, Martin G. Pomper, and Michael R. Zalutsky. “A third generation PSMA-targeted agent [211At]YF2: Synthesis and in vivo evaluation.” Nucl Med Biol 134–135 (2024): 108916. https://doi.org/10.1016/j.nucmedbio.2024.108916.
- Obata, Honoka, Mikako Ogawa, and Michael R. Zalutsky. “DNA Repair Inhibitors: Potential Targets and Partners for Targeted Radionuclide Therapy.” Pharmaceutics 15, no. 7 (July 11, 2023). https://doi.org/10.3390/pharmaceutics15071926.
- Feng, Yutian, Rebecca Meshaw, Xiao-Guang Zhao, Stephen Jannetti, Ganesan Vaidyanathan, and Michael R. Zalutsky. “Effective Treatment of Human Breast Carcinoma Xenografts with Single-Dose 211At-Labeled Anti-HER2 Single-Domain Antibody Fragment.” J Nucl Med 64, no. 1 (January 2023): 124–30. https://doi.org/10.2967/jnumed.122.264071.
- Rowe, S. P., R. A. Werner, T. Garg, A. Gafita, A. F. Voter, M. S. Sadaghiani, M. C. Markowski, et al. “Small Molecules as Vectors for Radiopharmaceutical Therapy.” In Radiopharmaceutical Therapy, 349–67, 2023. https://doi.org/10.1007/978-3-031-39005-0_17.