Evaluation of radiolabeled (hetero)aromatic analogues of N-(2-diethylaminoethyl)-4-iodobenzamide for imaging and targeted radionuclide therapy of melanoma.
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.
Chezal
Jean-Michel
JM
University Clermont 1, Clermont-Ferrand, France.
Papon
Janine
J
Labarre
Pierre
P
Lartigue
Claire
C
Galmier
Marie-Josephe
MJ
Decombat
Caroline
C
Chavignon
Olivier
O
Maublant
Jean
J
Teulade
Jean-Claude
JC
Madelmont
Jean-Claude
JC
Moins
Nicole
N
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
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