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99m Tc‐DTPA‐Amino Acids Conjugate as Specific SPECT Pharmaceuticals for Tumor Imaging
Author(s) -
Sinha Deepa,
Shukla Gauri,
Tiwari Anjani K.,
Chaturvedi Shubhra,
Chuttani Krishna,
Chandra Harish,
Mishra Anil K.
Publication year - 2009
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2009.00839.x
Subject(s) - chemistry , biodistribution , conjugate , amide , tryptophan , amino acid , radiochemistry , stereochemistry , biochemistry , in vitro , mathematical analysis , mathematics
99m Tc‐Diethylene triamine pentaacetic acid‐bis (amide) conjugates have been synthesized and evaluated as a potential radiopharmaceutical for tumor imaging. The compounds were synthesized by the condensation reaction of DTPA bis(anhydride) with different l ‐amino acids (methyl tryptophan, and 5‐hydroxy tryptophan) and were characterized on the basis of IR, NMR, and Mass spectroscopy. 99m Tc‐labeled compounds were found stable for about 24 h under physiological conditions with more than 95% radiolabeling yield. Blood kinetic studies of all these complexes showed a bi‐exponential pattern as well as quick wash out from the blood circulation. The biological t 1/2 (F) and t 1/2 (S) were found to be 20 ± 0.001 min for DTPA‐(Me‐Trp) 2 and 18 ± 0.001 min for DTPA‐(5HT) 2 and t 1/2 (slow) 5 h 45 min ± 0.001, 5 h 30 ± 0.001 min for DTPA‐(Me‐Trp) 2 , and DTPA‐(5HT) 2 , respectively. Imaging and biodistribution studies were performed in mice bearing Ehrlich ascites tumor (EAT) tumors in right thigh. Radioconjugate derived from l ‐5‐hydroxytryptophan exhibited remarkable localization at tumor site; whereas radiotracer derived from l ‐methyl tryptophan shows relatively less accumulation at the tumor site. Tumor‐to‐muscles ratios were 5.07 ± 0.001, and 4.2 ± 0.001 at 1 and 4 h for 99m Tc‐DTPA‐(Me trp) 2 and 4.97 ± 0.001 and 5.8 ± 0.001 at 1 and 4 h after postinjection for 99m Tc‐DTPA‐(5HT) 2 , respectively. The preliminary results with these amino acid based ligands are encouraging to carrying out further in vivo experiments for targeted tumor imaging.