The radiopharmaceutical meta-iodobenzylguanidine (MIBG) has been used in the detection and therapy of neuroendocrine tumors, especially neuroblastoma and pheochromocytoma. Although it is a satisfactory agent for diagnostic applications, the outcome of MIBG therapy is inadequate. The goal of this proposal is to develop an agent which is metabolically more stable, clears faster from normal tissues, and yet is sequestered and retained in tumor. The initial objectives of this proposal are to develop synthetic methods for the preparation of various radioiodinated and [At-211]-labeled MIBG derivatives and to systematically evaluate them in vitro and in vivo. The structural alterations planned include introduction of chlorine, bromine, iodine, nitro and sulfonic acid moieties at the 4-position in the benzene ring of MIBG and replacement of the benzene ring itself with a pyridine ring. Solid-phase synthetic methods will be developed for promising agents. The uptake and retention kinetics in vitro and the effect of several pharmacological agents will be studied using a panel of neuroblastoma, pheochromocytoma and medulloblastoma cell lines. Although not a neuroendocrine tumor, specific uptake of MIBG has been demonstrated in several human medulloblastoma cell lines, and this neoplasm is well suited for [At-211]-therapy. The therapeutic potential of these new [I-131]- and [At-211]-labeled MIBG analogues will be evaluated using thymidine uptake and clonogenic assays in monolayer and spheroid models. Tissue distribution of these agents will be determined in normal mice and athymic mice hosting neuroblastoma, pheochromocytoma, and medulloblastoma xenografts. Strategies to augment tumor-to-normal tissue ratios will be investigated. The outcome of this study should help improve the endoradiotherapy of neuroendocrine tumors and possibly of medulloblastoma.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Stone, Helen B
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Duke University
Schools of Medicine
United States
Zip Code
Vaidyanathan, Ganesan; Affleck, Donna J; Alston, Kevin L et al. (2004) Catabolism of 4-fluoro-3-iodobenzylguanidine and meta-iodobenzylguanidine by SK-N-SH neuroblastoma cells. Nucl Med Commun 25:947-55
Vaidyanathan, G; Shankar, S; Zalutsky, M R (2001) Synthesis of ring- and side-chain-substituted m-iodobenzylguanidine analogues. Bioconjug Chem 12:786-97
Vaidyanathan, G; Shankar, S; Affleck, D J et al. (2001) Biological evaluation of ring- and side-chain-substituted m-iodobenzylguanidine analogues. Bioconjug Chem 12:798-806
Vaidyanathan, G; Affleck, D J; Cavazos, C M et al. (2000) Radiolabeled guanine derivatives for the in vivo mapping of O(6)-alkylguanine-DNA alkyltransferase: 6-(4-[(18)F]Fluoro-benzyloxy)-9H-purin-2-ylamine and 6-(3-[(131)I]Iodo-benzyloxy)-9H-purin-2-ylamine. Bioconjug Chem 11:868-75
Vaidyanathan, G; Affleck, D; Welsh, P et al. (2000) Radioiodination and astatination of octreotide by conjugation labeling. Nucl Med Biol 27:329-37
Vaidyanathan, G; Zalutsky, M R; DeGrado, T R (1998) Iodopyridine-for-iodobenzene substitution for use with low molecular weight radiopharmaceuticals: application to m-iodobenzylguanidine. Bioconjug Chem 9:758-64
Vaidyanathan, G; Zalutsky, M R (1998) Preparation of 5-[131I]iodo- and 5-[211At]astato-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) uracil by a halodestannylation reaction. Nucl Med Biol 25:487-96