title: Synthesis and evaluation of novel radioiodinated benzamides for malignant melanoma.
abstract: The imaging potential of a series of [123I]benzamides was studied in mice bearing B16F0 melanoma tumors. Compound [123I]25 exhibited tumor uptake >8 %ID/g at 1 h, while that of [123I]14d and [123I]25 reached a maximum of 9-12 %ID/g at 6 h. Standardized uptake values of [123I]14d were higher than 100 between 24 and 72 h after injection. In haloperidol treated animals, the tumor uptake of [123I]14d was not significantly different to controls, while significant reduction of [123I]25 uptake was observed, supporting that [123I]14d uptake relates to melanin interaction, whereas part of the mechanism of [123I]25 uptake is related to its sigma 1-receptor affinity. Benzamides 14d and 25, which display rapid and high tumor uptake, appear to be promising imaging agents for melanoma detection, while 14d, which displays a long lasting and high melanoma/nontarget ratio, is more suitable for evaluation as a potential radiotherapeutic.
authors.affiliation: Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, PMB 1 Menai N.S.W. 2234, Sydney, Australia.
authors.forename: Tien Q
authors.initials: TQ
authors.lastname: Pham
authors.forename: Ivan
authors.initials: I
authors.lastname: Greguric
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.forename: Paula
authors.initials: P
authors.lastname: Berghofer
authors.forename: Patrice
authors.initials: P
authors.lastname: Ballantyne
authors.forename: Janette
authors.initials: J
authors.lastname: Chapman
authors.forename: Filomena
authors.initials: F
authors.lastname: Mattner
authors.forename: Branko
authors.initials: B
authors.lastname: Dikic
authors.forename: Timothy
authors.initials: T
authors.lastname: Jackson
authors.forename: Christian
authors.initials: C
authors.lastname: Loc'h
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
mesh_terms: D000083:Acetanilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D001667:Binding, Competitive; D006220:Haloperidol / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008024:Ligands; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014183:Transplantation, Heterologous
chemical_list: C523413:4-acetamido-N-(4-(N-butyl-N-methylamino)butyl)-5-iodo-2-methoxybenzamide; D000083:Acetanilides; D001549:Benzamides; D007457:Iodine Radioisotopes; D008024:Ligands; C523414:N-(1-(2-fluoroethyl)piperidin-4-yl)-4-iodobenzamide; D010880:Piperidines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma; D006220:Haloperidol