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.

Paclitaxel-loaded folate-coated long circulating and pH-sensitive liposomes as a potential drug delivery system: A biodistribution study

“…For liposome radiolabeling, the lipid DSPE-PEG 2000 -DTPA was used since it is well known that 99m Tc generates a stable complex with chelating agents, such as DTPA, for image purposes [23,41,43,44]. The results showed a high radiochemical purity and stability (over to 90%), up to 24 h after radiolabeling.…”

“…99m Tc-PTX was prepared using the methodology described by Monteiro et al [14,26] and was used as a comparative group with the liposomal preparations presented in these studies [3,16]. For liposome radiolabeling, the lipid DSPE-PEG 2000 -DTPA was used since it is well known that 99m Tc generates a stable complex with chelating agents, such as DTPA, for image purposes [23,41,43,44]. The results showed a high radiochemical purity and stability (over to 90%), up to 24 h after radiolabeling.…”

99m Tc-labeled estradiol as an estrogen receptor probe: Preparation and preclinical evaluation

“…To meet the need for quantifiable targeting to estrogen receptor sites, we focused on linear polyaminopolycarboxylic acid chelating agents [20]. We intended to enhance the water solubility of the estrogen receptor probe by introducing DTPA groups, expecting to minimize the intrahepatic metabolism.…”

Design, synthesis and preliminary evaluation of a novel SPECT DTPA-bis-triazaspirodecanone conjugate for D2receptor imaging

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