Structure distribution relationship of iodine-123-iodobenzamides as tracers for the detection of melanotic melanoma.
The influence of systematic structure variations on the biodistribution of positional isomers of N-(N'-dialkylaminoethylene)-[123I]iodobenzamide (ABA) derivatives in melanoma-bearing animals was investigated.


METHODS
Radioiodination of six bromo benzamide precursors was achieved by Cu(1)-assisted nonisotopic halogen exchange. Organ distribution, scintigraphic and metabolic studies were performed in nude mice bearing a human melanotic MM (SK-MEL 25). A patient suffering from melanotic melanoma underwent scintigraphy with a [123I]iodobenzamide.


RESULTS
High radiochemical yields of 80%-95% and specific activities of > 5 TBq/ mumole were obtained. Animal studies revealed specific tumor uptake of all compounds with longest retention of the most lipophilic derivative p-[123I]ABA 2-2. At shorter times, however, o-[123I]ABA 2-2 exhibited the highest tumor uptake (8.9% ID/g, 1 hr p.i., 10.9% ID/g, 4 hr p.i.). Metabolization of o-[123I]ABA 2-2, mainly to o-[123I]iodohippuric acid (OIH), followed by fast renal excretion of the metabolites lead to tumor/nontumor ratios (T/NT) of > 400 for tumor/blood, and > 70 for tumor/liver at 48 h p.i. Unknown metastases could be localized in a patient using o-[123I]ABA 2-2.


CONCLUSIONS
The effects of the structure variation of iodobenzamides on their lipophilicity, metabolism and thus pharmacokinetics lead to the suggestion of o-[123I]ABA 2-2 as a favorable melanoma imaging agent.
Clinic for Nuclear Medicine, Westfälische Wilhelms-Universität Münster, Germany.
W
W
Brandau
T
T
Niehoff
P
P
Pulawski
M
M
Jonas
K
K
Dutschka
J
J
Sciuk
H H
HH
Coenen
O
O
Schober
D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics; D006801:Humans; D007457:Iodine Radioisotopes; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000556:secondary; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D012878:Skin Neoplasms / Q000000981:diagnostic imaging*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D001549:Benzamides; D007457:Iodine Radioisotopes