Synthesis of [DTPA-bis(D-ser)] chelate (DBDSC): an approach for the design of SPECT radiopharmaceuticals based on technetium.
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.
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi, India. raunak_varshney@yahoo.com
Raunak
R
Varshney
Swarndeep K
SK
Sethi
Puja P
PP
Hazari
Krishna
K
Chuttani
Sachin
S
Soni
Marilyn D
MD
Milton
Anil K
AK
Mishra
D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011817:Rabbits; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012694:Serine / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D016284:Technetium Tc 99m Pentetate / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon
D002614:Chelating Agents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C579621:technetium 99m (DTPA-bis(serine)); D012694:Serine; D016284:Technetium Tc 99m Pentetate