title: Evaluation of radiolabeled (hetero)aromatic analogues of N-(2-diethylaminoethyl)-4-iodobenzamide for imaging and targeted radionuclide therapy of melanoma.
abstract: Targeted radionuclide therapy using radioiodinated compounds with a specific affinity for melanoma tissue is a promising treatment for disseminated melanoma, but the candidate with the ideal kinetic profile remains to be discovered. Targeted radionuclide therapy concentrates the effects on tumor cells, thereby increasing the efficacy and decreasing the morbidity of radiotherapy. In this context, analogues of N-(2-diethylaminoethyl)-4-iodobenzamide (BZA) are of interest. Various (hetero)aromatic analogues 5 of BZA were synthesized and radioiodinated with (125)I, and their biodistribution in melanoma-bearing mice was studied after i.v. administration. Most [ (125)I] 5-labeled compounds appeared to bind specifically and with moderate-to-high affinity to melanoma tumor. Two compounds, 5h and 5k, stood out with high specific and long-lasting uptake in the tumor, with a 7- and 16-fold higher value than BZA at 72 h, respectively, and kinetic profiles that makes them promising agents for internal targeted radionuclide therapy of melanoma.
authors.affiliation: University Clermont 1, Clermont-Ferrand, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Chezal
authors.forename: Janine
authors.initials: J
authors.lastname: Papon
authors.forename: Pierre
authors.initials: P
authors.lastname: Labarre
authors.forename: Claire
authors.initials: C
authors.lastname: Lartigue
authors.forename: Marie-Josephe
authors.initials: MJ
authors.lastname: Galmier
authors.forename: Caroline
authors.initials: C
authors.lastname: Decombat
authors.forename: Olivier
authors.initials: O
authors.lastname: Chavignon
authors.forename: Jean
authors.initials: J
authors.lastname: Maublant
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Teulade
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Madelmont
authors.forename: Nicole
authors.initials: N
authors.lastname: Moins
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D008297:Male; D008543:Melanins / Q000737:chemistry; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D001549:Benzamides; D007457:Iodine Radioisotopes; D008543:Melanins; C530302:N-(2-diethylaminoethyl)-6-iodoquinoline-2-carboxamide; C530303:N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide; D011804:Quinolines; D011810:Quinoxalines; D019275:Radiopharmaceuticals