Effect of carboxylation of N-terminal phenylalanine of 111In-DTPA (diethylenetriaminepentaacetic acid)octreotide on accumulation of radioactivity in kidney

For purpose of reducing renal accumulation of radioactivity of a known radiopharmaceutical agent, i.e., In-111-DTPA (diethylenetriaminepentaacetic acid)-D-Phe(1)-octreotide, a derivative in which p-carboxy-L-phenylalanine is substituted for D-Phe(1) was synthesized. Biodistribution study of the resultant compound having carboxy-substituted L-Phe(1) revealed that the renal accumulation was significantly lower than that of control compound having unsubstituted L-Phe(1), demonstrating that the presence of negative charge on the N-terminal amino acid of octreotide is effective to reduce the renal accumulation. This effect can be attributed to the reduction of lipophilicity and also the repulsive force arisen from the negative charge of renal brush border membrane.