title: SIMS microscopy imaging of the intratumor biodistribution of metaiodobenzylguanidine in the human SK-N-SH neuroblastoma cell line xenografted into nude mice.
abstract: 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 use of secondary ion mass spectrometry (SIMS) microscopy, a technique capable of mapping any chemical element within a biological specimen, to determine 127I-MIBG biodistribution in human neuroblastoma SK-N-SH xenografted into nude mice. Highly specific images of 127I-MIBG biodistribution were mapped within the tumor after in vivo administration of the drug and sample processing with cryotechniques (high-speed freezing and cryo-embedding), which prevent MIBG diffusion from original sites of uptake. We showed that the biodistribution of the tracer was highly nonuniform within the tumor. At the cellular level, most of the drug accumulated in the cytosol and perinuclear areas. In contrast, chemical sample processing provided not only a considerable loss in sensitivity due to passive diffusion of the drug in the organic solvents, but 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 carrier-free.
authors.affiliation: Equipe de Microscopie Ionique, INSERM U 66, Institut Gustave-Roussy, Villejuif, France.
authors.forename: J
authors.initials: J
authors.lastname: Clerc
authors.forename: S
authors.initials: S
authors.lastname: Halpern
authors.forename: C
authors.initials: C
authors.lastname: Fourré
authors.forename: F
authors.initials: F
authors.lastname: Omri
authors.forename: C
authors.initials: C
authors.lastname: Briançon
authors.forename: J
authors.initials: J
authors.lastname: Jeusset
authors.forename: P
authors.initials: P
authors.lastname: Fragu
mesh_terms: D019797:3-Iodobenzylguanidine; D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003287:Contrast Media; D006801:Humans; D007456:Iodine Isotopes; D007462:Iodobenzenes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D008853:Microscopy; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy / Q000532:radiotherapy*; D011878:Radiotherapy / Q000379:methods; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D007456:Iodine Isotopes; D007462:Iodobenzenes; D019797:3-Iodobenzylguanidine