ASSESSING INTRATUMOR DISTRIBUTION AND UPTAKE WITH MBBG VERSUS MIBG IMAGING AND TARGETING XENOGRAFTED PC12-PHEOCHROMOCYTOMA CELL-LINE

The heterogeneity of tumor uptake is likely to substantially limit the effectiveness of metaiodobenzylguanidine (MIBG) therapy. This study w as done to establish whether metabromobenzylguanidine (MBBG) can targe t neuroendocrine tumors and to provide intratumor biodistribution and uptake information in comparison to MIBG. Methods: MBBG and MIBG tumor uptake and kinetic studies were performed in experimental PC-12 pheoc hromocytoma grown in nude mice. Intratumor distribution studies were p erformed using autoradiography and secondary ion mass spectrometry (SI MS) microscopy, because the latter technique can detect and potentiall y quantify both drugs concomitantly within the same tumor specimen. Re sults: MBBG uptake in PC12 tumors was early (2 hr) and intense (80% ID /g). Retention values were similar for both drugs 24 hr postinjection. At the cellular level, MBBG mostly accumulated in the cytosol. At the multicellular level, cells exhibited staining, but in many areas, SIM S images of both drugs were not spatially correlated. Conclusion: MBBG targeted experimental pheochromocytoma efficiently with high early up take values. Bromine-76-MBBG is a promising means of imaging and quant ifying tumor uptake with PET. Both drugs were localized in the cytosol , but the correlation between the two distributions, as assessed by th e values of the standardized local concentrations, was weak although s ignificant multicellularly.