Abstract |
(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.
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Authors | Deepa Sinha, Gauri Shukla, Anjani K Tiwari, Shubhra Chaturvedi, Krishna Chuttani, Harish Chandra, Anil K Mishra |
Journal | Chemical biology & drug design
(Chem Biol Drug Des)
Vol. 74
Issue 2
Pg. 159-64
(Aug 2009)
ISSN: 1747-0285 [Electronic] England |
PMID | 19614681
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amino Acids
- Radiopharmaceuticals
- tryptophan methyl ester
- Pentetic Acid
- Tryptophan
- 5-Hydroxytryptophan
- Technetium Tc 99m Pentetate
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Topics |
- 5-Hydroxytryptophan
(analogs & derivatives, chemistry, pharmacokinetics)
- Amino Acids
(chemistry)
- Animals
- Carcinoma, Ehrlich Tumor
(diagnostic imaging)
- Cell Line, Tumor
- Humans
- Mice
- Mice, Inbred BALB C
- Pentetic Acid
(analogs & derivatives, chemistry, pharmacokinetics)
- Rabbits
- Radiopharmaceuticals
(chemistry, pharmacokinetics)
- Technetium Tc 99m Pentetate
(chemistry)
- Tissue Distribution
- Tomography, Emission-Computed, Single-Photon
- Tryptophan
(analogs & derivatives, chemistry, pharmacokinetics)
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