99mTc-DTPA-amino acids conjugate as specific SPECT pharmaceuticals for tumor imaging.
(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.
Sinha
Deepa
D
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Shukla
Gauri
G
Tiwari
Anjani K
AK
Chaturvedi
Shubhra
S
Chuttani
Krishna
K
Chandra
Harish
H
Mishra
Anil K
AK
D006916:5-Hydroxytryptophan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D016284:Technetium Tc 99m Pentetate / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014364:Tryptophan / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics*
D000596:Amino Acids; D019275:Radiopharmaceuticals; C028129:tryptophan methyl ester; D004369:Pentetic Acid; D014364:Tryptophan; D006916:5-Hydroxytryptophan; D016284:Technetium Tc 99m Pentetate