A major asset in the use of radiolabeled antibodies is the ability to trace the agent in vivo and readily generate pharmacokinetic and radiation dosimetric information that can guide development of the therapeutic agents, define conditions for their optimal use, and serve as the basis for individualized treatment planning. The primary role of this core is to support the clinical trials in Projects 1 and 2 and the translational chemistry, radiochemistry and radiopharmaceutical development conducted in Project 3 and Core C by providing pharmacokinetic and dosimetric information for decision-making. Dosimetric support for preclinical studies in Projects 1 and 2 is also provided. Methodology and software have been developed that converts regional counts obtained by quantitative imaging or biodistribution studies to macroscopic tissue radiation doses; these estimates have been validated. Pharmacokinetic and dosimetric data for a variety of antibody-based radiopharmaceuticals has been generated and has served as the basis for the evolution to the proposed use of DOTA-peptide radiopharmaceuticals because of their unusually favorable therapeutic index. In order to fulfill past requirements, methods for quantitative imaging, region of interest and background definition, and attenuation and coincidence correction have been implemented. Because the proposed protocols need to push tumor radiation to the maximum in order to attempt to fulfill the goal of curative radioimmunotherapy, treatment planning requires implementation of patient-specific dosimetry that accounts for major tissues that may be dose-limiting. This requires additional refinements to existing methods in order to further account for source depth, tissue overlapping, anatomic location and volume effects, radionuclide energy distribution, and non-uniform radionuclide deposition, etc. The goal is to develop a comprehensive radioimmunotherapy planning System based on patient-specific dosimetry and tissue dose response function.
| Schellinger, Joan G; Kudupudi, Avinash; Natarajan, Arutselvan et al. (2012) A general chemical synthesis platform for crosslinking multivalent single chain variable fragments. Org Biomol Chem 10:1521-6 |
| Saludes, Jonel P; Natarajan, Arutselvan; DeNardo, Sally J et al. (2010) The remarkable stability of chimeric, sialic acid-derived alpha/delta-peptides in human blood plasma. Chem Biol Drug Des 75:455-60 |
| Kumaresan, Pappanaicken R; Luo, Juntao; Lam, Kit S (2009) On-demand cleavable linkers for radioimmunotherapy. Methods Mol Biol 539:191-211 |
| DeNardo, G L; Mirick, G R; Hok, S et al. (2009) Molecular specific and cell selective cytotoxicity induced by a novel synthetic HLA-DR antibody mimic for lymphoma and leukemia. Int J Oncol 34:511-6 |
| Balhorn, Rod; Hok, Saphon; DeNardo, Sally et al. (2009) Hexa-arginine enhanced uptake and residualization of selective high affinity ligands by Raji lymphoma cells. Mol Cancer 8:25 |
| Sulchek, Todd; Friddle, Raymond; Ratto, Timothy et al. (2009) Single-molecule approach to understanding multivalent binding kinetics. Ann N Y Acad Sci 1161:74-82 |
| DeNardo, Gerald L; DeNardo, Sally J; Balhorn, Rod (2008) Systemic radiotherapy can cure lymphoma: a paradigm for other malignancies? Cancer Biother Radiopharm 23:383-97 |
| DeNardo, Gerald L; Natarajan, Arutselvan; Hok, Saphon et al. (2008) Nanomolecular HLA-DR10 antibody mimics: A potent system for molecular targeted therapy and imaging. Cancer Biother Radiopharm 23:783-96 |
| Natarajan, Arutselvan; Xiong, Cheng-Yi; Gruettner, Cordula et al. (2008) Development of multivalent radioimmunonanoparticles for cancer imaging and therapy. Cancer Biother Radiopharm 23:82-91 |
| Lehmann, Joerg; Natarajan, Arutselvan; Denardo, Gerald L et al. (2008) Short communication: nanoparticle thermotherapy and external beam radiation therapy for human prostate cancer cells. Cancer Biother Radiopharm 23:265-71 |
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