Radioiodinated N-(alkylaminoalkyl)-substituted 4-methoxy-, 4-hydroxy-, and 4-aminobenzamides: biological investigations for the improvement of melanoma-imaging agents.
The syntheses and radiolabelling of 27 new N-(alkylaminoalkyl)-4-methoxy-, -4-hydroxy-, and -4-aminobenzamides are described and evaluated in C57B1/6 mice with subcutaneously transplanted B16 melanoma in order to screen the optimal chemical structure for melanoma scintigraphy. Using T1(TFA)3 for 131I- labelling, a series of radioiodinated 4-methoxy benzamide derivatives proved to exhibit superior melanoma uptake with outstanding melanoma/non-target-tissue ratios. From the benzamide derivatives tested, N-(2-(1'-piperidinyl)ethyl-3-[131I]iodo-4-methoxybenzamide and N-(2-diethylaminoethyl)-3-[131I]iodo-4-methoxybenzamide demonstrated best results. The introduction of 4-hydroxy and 4-amino groups led to less favourable benzamides. While the former compounds showed little melanoma uptake, the latter revealed unfavourable melanoma/non-target-tissue ratios. Additionally, it could be shown that an amino group was inevitably necessary for melanoma uptake, and that dialkylation of the amide nitrogen and replacing CONH by CH2NH revealed less advantageous results.
Mohammed
A
A
Department of Nuclear Medicine, University of Heidelberg, Germany.
Nicholl
C
C
Titsch
U
U
Eisenhut
M
M
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D008810:Mice, Inbred C57BL; D011877:Radionuclide Imaging; D013329:Structure-Activity Relationship
D001549:Benzamides; D007457:Iodine Radioisotopes