Synthesis of [DTPA-bis(D-ser)] Chelate (DBDSC): An Approach for the Design of SPECT Radiopharmaceuticals Based on Technetium

Raunak      Varshney; Swarndeep      K. Sethi; Puja      P. Hazari; Krishna      Chuttani; Sachin      Soni; Marilyn      D. Milton; Anil      K. Mishra

doi:10.2174/1874471011205040348

Abstract

D-Serine is a physiological coagonist of the N-methyl D-aspartate (NMDA) type of glutamate receptor-a key excitatory neurotransmitter receptor in the brain. D-Serine appears to be a part of the synapse through a variety of transporters located on both neurons and astrocytes. The development of 99mTc radiolabeled amino acid based radiopharmaceuticals for imaging a variety of tumors has found to be useful in diagnostic imaging. Diethylene triamine penta acetic acid (DTPA) is one of the most well-known chelating reagent for the production of stable complexes with various heavy metal ions. We have synthesized [DTPA-bis(D-ser)] in 90% yield and analyzed the chelate by spectroscopic techniques. The DBDSC chelate binds to 99mTc with high efficiency at ambient temperature. The resulting chelate is stable under physiological conditions (37oC, pH=7.4) for at least 24 h after radiocomplexation. The receptor binding studies of 99mTc-[DTPA-bis(D-ser)] in established lung adeno carcinoma A549 exhibited Kd value to be 26nM. A549 Tumor in athymic mice was accumulated in the γ-images. The major accumulation of the radiotracer was observed in tumor, followed by kidneys. 99mTc-[DTPA-bis(D-ser)] has promising utility as SPECT-radiopharmaceutical.

Keywords: DTPA, D-Ser, NMDA Receptor, Radiopharmaceuticals, SPECT, 99mTc.

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