title: Synthesis, in vitro binding and biodistribution in B16 melanoma-bearing mice of new iodine-125 spermidine benzamide derivatives.
abstract: In the course of our investigations aimed at improving the biological characteristics of iodobenzamides for melanoma therapeutic applications, four new derivatives containing a spermidine chain have been prepared and radiolabeled with (125)I. In vitro studies showed that all compounds displayed high affinity for melanin superior to the reference compound BZA, thus validating our experimental approach. In vivo biodistribution was investigated in B16 melanoma-bearing mice. All four compounds, particularly benzamide 3, showed accumulation in the tumor, but lower, however, than that of BZA. Moreover, high concentrations of radioactivity in other organs, namely, the liver and lung, demonstrated nonspecific tumoral uptake. In view of these results, compounds 1 2 3 4 do not appear to be suitable radiopharmaceuticals for melanoma radionuclide therapy.
authors.affiliation: INSERM UMR 484, BP 184, 63000 Clermont-Ferrand cedex, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Moreau
authors.forename: Janine
authors.initials: J
authors.lastname: Papon
authors.forename: Pierre
authors.initials: P
authors.lastname: Labarre
authors.forename: Nicole
authors.initials: N
authors.lastname: Moins
authors.forename: Michèle
authors.initials: M
authors.lastname: Borel
authors.forename: Martine
authors.initials: M
authors.lastname: Bayle
authors.forename: Bernadette
authors.initials: B
authors.lastname: Bouchon
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Madelmont
mesh_terms: D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001822:Body Burden; D045744:Cell Line, Tumor; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000532:radiotherapy; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011485:Protein Binding; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D013095:Spermidine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D001549:Benzamides; D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; D008543:Melanins; D019275:Radiopharmaceuticals; D013095:Spermidine