Synthesis and evaluation of novel radioiodinated benzamides for malignant melanoma.
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.
Pham
Tien Q
TQ
Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, PMB 1 Menai N.S.W. 2234, Sydney, Australia.
Greguric
Ivan
I
Liu
Xiang
X
Berghofer
Paula
P
Ballantyne
Patrice
P
Chapman
Janette
J
Mattner
Filomena
F
Dikic
Branko
B
Jackson
Timothy
T
Loc'h
Christian
C
Katsifis
Andrew
A
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
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