Effect of carboxyl-group of D-glutamic acid or γ-carboxy-D-glutamic acid as N-terminal amino acid of 111In-diethylenetriaminepentaacetic acid-octreotide on accumulation of radioactivity in kidney

Abstract

To establish a strategy for developing 111In- diethylenetriaminepentaacetic acid (111In-DTPA)-octreotide, a diagnostic radiopharmaceutical agent for tumors, with reduced non-specific renal radio-accumulation, the compounds having D-glutamic acid (Glu) or γ-carboxy-D-glutamic acid (carboxy-Glu) as the N-terminal amino acid were examined for in vivo radio-distribution. Compounds carrying Glu and carboxy-Glu containing one and two negative charges, respectively, showed lower renal radio-accumulation than that carrying D-phenylalanine. It was revealed that the introduction of a negative charge reduces the renal radio-accumulation independently from the number of negative charges. The present result can be a clue for the development of 111In-DTPA-octreotides with reduced the renal radio-accumulation. © 2007 Pharmaceutical Society of Japan.