Analogs of alicyclic alpha-amino acids--effect of ring size and side chain on tumor accumulation

We studied the tumor-localizing characteristics of alicyclic alpha-amino acid analogs (a-j) without alpha-hydrogen, because of the selective affinity of synthetic nonmetabolizing amino acids such as 1-aminocyclopentanecarboxylic acid (ACPC) and alpha-aminoisobutyric acid alpha-AIB) to tumor tissues. Ten different alicyclic alpha-amino acids (a-j) were labeled with 14C using a modified Bücherer synthesis for amino acids. The tissue distributions and whole-body autoradiographic study of these 14C-labeled alicyclic alpha-amino acid analogs (a-j) were investigated in mice bearing Ehrlich tumor. These results showed that the tumor uptakes and tumor to tissue concentration ratios increased with decreasing ringsize in homologous series (8- through 4-membered ring systems) and alicyclic alpha-amino acid analogs containing 3- or 4-methyl group had the higher tumor to tissue concentration ratios. On the other hand, alicyclic alpha-amino acid analogs containing 2-methyl group and 4-phenyl group showed the lower tumor uptakes and the lower tumor to tissue concentration ratios. These results suggest that the small ringsize alicyclic alpha-amino acid analogs containing 3-methyl group such as 3-methyl-1-aminocyclopentanecarboxylic acid (3-MeACPC) may be effective for the early detection of tumors.