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.
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 of Radiation Oncology
- Professor in Pathology
- Member of the Duke Cancer Institute
Contact Information
- Office Location: 311 Research Drive, 161H Bryan Res Bldg, Durham, NC 27710
- Office Phone: (919) 684-7708
- Email Address: zalut001@mc.duke.edu
- Websites:
Education
- M.A. Washington University in St. Louis, 1972
- Ph.D. Washington University in St. Louis, 1974
Courses Taught
- PATHOL 793: Research Independent Study
Representative Publications
- 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.” Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine 64, no. 1 (January 2023): 124–30. https://doi.org/10.2967/jnumed.122.264071.
- Feng, Yutian, Samantha M. Sarrett, Rebecca L. Meshaw, Ganesan Vaidyanathan, Mike A. Cornejo, Brian M. Zeglis, and Michael R. Zalutsky. “Site-Specific Radiohalogenation of a HER2-Targeted Single-Domain Antibody Fragment Using a Novel Residualizing Prosthetic Agent.” J Med Chem 65, no. 22 (November 24, 2022): 15358–73. https://doi.org/10.1021/acs.jmedchem.2c01331.
- Schaal, Jeffrey L., Jayanta Bhattacharyya, Jeremy Brownstein, Kyle C. Strickland, Garrett Kelly, Soumen Saha, Joshua Milligan, et al. “Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours.” Nat Biomed Eng 6, no. 10 (October 2022): 1148–66. https://doi.org/10.1038/s41551-022-00949-4.
- Zhou, Zhengyuan, Michael R. Zalutsky, and Satish K. Chitneni. “Stapled peptides as scaffolds for developing radiotracers for intracellular targets: Preliminary evaluation of a radioiodinated MDM2-binding stapled peptide in the SJSA-1 osteosarcoma model.” Bioorg Med Chem Lett 66 (June 15, 2022): 128725. https://doi.org/10.1016/j.bmcl.2022.128725.