SIMS MICROSCOPY IMAGING OF THE INTRATUMOR BIODISTRIBUTION OF METAIODOBENZYLGUANIDINE IN THE HUMAN SK-N-SH NEUROBLASTOMA CELL-LINE XENOGRAFTED INTO NUDE-MICE

Microdosimetric evaluations of targeted radiotherapy of neuroblastoma with metaiodobenzylguanidine (MIBG) require precise assessment of the intracellular and intratumor distribution of the drug. We report the u se of secondary ion mass spectrometry (SIMS) microscopy, a technique c apable of mapping any chemical element within a biological specimen, t o determine I-127-MIBG biodistribution in human neuroblastoma SK-N-SH xenografted into nude mice. Highly specific images of I-127-MIBG biodi stribution were mapped within the tumor after in vivo administration o f the drug and sample processing with cryotechniques (high-speed freez ing and cryo-embedding), which prevent MIBG diffusion from original si tes of uptake. We showed that the biodistribution of the tracer was hi ghly nonuniform within the tumor. At the cellular level, most of the d rug accumulated in the cytosol and perinuclear areas. In contrast, che mical sample processing provided not only a considerable loss in sensi tivity due to passive diffusion of the drug in the organic solvents, b ut also artefactual images mainly due to MIBG redistribution onto the cell nuclei. Based on our findings in this SK-N-SH experimental tumor model, we suggest that MIBG should be attached to long-range emitters, in the hope of irradiating the many tumorous areas that remain carrie r-free.