Synthesis of [DTPA-bis(D-ser)] chelate (DBDSC): an approach for the design of SPECT radiopharmaceuticals based on technetium.

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.

• Authors: Raunak Varshney, Swarndeep K Sethi, Puja P Hazari, Krishna Chuttani, Sachin Soni, Marilyn D Milton, Anil K Mishra
• Journal: Current radiopharmaceuticals (Curr Radiopharm) Vol. 5 Issue 4 Pg. 348-55 (Oct 2012) ISSN: 1874-4729 [Electronic] United Arab Emirates
• PMID: 22642421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chelating Agents
• Organotechnetium Compounds
• Radiopharmaceuticals
• technetium 99m (DTPA-bis(serine))
• Serine
• Technetium Tc 99m Pentetate

Topics

• Animals
• Chelating Agents (chemical synthesis, pharmacokinetics)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasms (diagnostic imaging, metabolism)
• Organotechnetium Compounds (chemical synthesis, pharmacokinetics)
• Rabbits
• Radioligand Assay
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics)
• Serine (chemical synthesis, pharmacokinetics)
• Technetium Tc 99m Pentetate (chemical synthesis, pharmacokinetics)
• Tomography, Emission-Computed, Single-Photon