title: Meta-iodobenzylguanidine derivatives containing a second guanidine moiety.
abstract: Radioiodinated meta-iodobenzylguanidine (MIBG) is used in the diagnosis and therapy of various neuroendocrine tumors. To investigate whether an additional guanidine function in the structure of MIBG will yield analogues that may potentially enhance tumor-to-target ratios, two derivatives-one with a guanidine moiety and another with a guanidinomethyl group at the 4-position of MIBG-were prepared. In the absence of any uptake-1 inhibiting conditions, the uptake of 4-guanidinomethyl-3-[(131)I]iodobenzylguanidine ([(131)I]GMIBG) by SK-N-SH cells in vitro was 1.7+/-0.1% of input counts, compared to a value of 40.3+/-1.4% for [(125)I[MIBG suggesting that guanidinomethyl group at the 4-position negated the biological properties of MIBG. On the other hand, 4-guanidino-3-[(131)I]iodobenzylguanidine ([(131)I]GIBG) had an uptake (5.6+/-0.3%) that was 12-13% that of [(125)I]MIBG (46.1+/-2.7%), and the ratio of uptake by control over DMI-treated (nonspecific) cultures was higher for [(131)I]GIBG (20.9+/-0.3) than [(125)I]MIBG itself (15.0+/-2.7). The exocytosis of [(131)I]GIBG and [(125)I]MIBG from SK-N-SH cells was similar. The uptake of [(131)I]GIBG in the mouse target tissues, heart and adrenals, as well as in a number of other tissues was about half that of [(125)I]MIBG. These results suggest that substitution of guanidine functions, especially a guanidinomethyl group, in MIBG structure may not be advantageous.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA. ganesan.v@duke.edu
authors.forename: Ganesan
authors.initials: G
authors.lastname: Vaidyanathan
authors.forename: Sriram
authors.initials: S
authors.lastname: Shankar
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Affleck
authors.forename: Kevin
authors.initials: K
authors.lastname: Alston
authors.forename: Joseph
authors.initials: J
authors.lastname: Norman
authors.forename: Philip
authors.initials: P
authors.lastname: Welsh
authors.forename: Holly
authors.initials: H
authors.lastname: LeGrand
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D019797:3-Iodobenzylguanidine / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006146:Guanidines / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D051379:Mice; D015394:Molecular Structure; D014018:Tissue Distribution
chemical_list: D006146:Guanidines; D007457:Iodine Radioisotopes; D019797:3-Iodobenzylguanidine