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The novel tetraaza macrobicyclic chelator 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-2,10-dione ( TBPD) and pentaaza macrotricyclic chelator 9-oxa-3,6,12,15,21-pentaazatricyclo[15,3,2,1]trieicos-1(21),17,19-triene-2,7,11,16-tetradione ( OPTT) were synthesized, characterized, and radiolabeled with 99mTc to produce 99mTc- TBPD and 99mTc- OPTT. These radiolabeled complexes were prepared with high radiolabeling yield, radiochemical purity, and good in vitro stability up to 24 h. The labeling efficiency of 99mTc- TBPD and 99mTc- OPTT was found 98% and 97%. In vitro serum stability of 99mTc- TBPD was found to be 95.2%, while that of 99mTc- OPTT 94.2% up to 24 h. Blood kinetics experiments of 99mTc-labeled complexes showed biphasic pattern of blood clearance. About 99.57 ± 0.89% activity of 99mTc- TBPD and 99.42 ± 0.88% activity of 9mTc- OPTT were cleared off blood stream at 24 h postadministration. The biological half-life of 99mTc- TBPD was observed: t1/2(F) 1 h 5 min and t1/2(S) 12 h and biological half-life of 99mTc- OPTT was observed: t1/2(F) 1 h 10 min and t1/2(S) 9 h 50 min, respectively. The biodistribution studies revealed that maximum uptake of 99mTc- TBPD was found in liver, concluded that excretory pathway is hepatobiliary, while that of 99mTc- OPTT was renal as well as hepatobiliary. The negligible activity observed in stomach confirming the stability of radiolabeled complex in biological milieu. In vitro cytotoxicity study of TBPD and OPTT did not show any considerable antiproliferative activity against cancer cells of human cervical SW756, HeLa, and glioblastoma U-87, U373 cell lines. [ABSTRACT FROM AUTHOR]

A bisphosphonate derivative DTPA-bis(alendronate) conjugate has been synthesized and evaluated as potential radiopharmaceutical for bone imaging. The compound was synthesized by the covalent coupling of DTPA-bis(anhydride) with alendronate and was char-acterized on the basis of IR, NMR and mass spectroscopy. It was labelled with 99mTc with 96% efficacy and was found stable for about 24 h under physiological conditions. Blood kinetic studies of 99mTc DTPA-bis(alendronate) showed a biexponential pattern as well as quick washout from the blood circulation. The biological t1/2(F) and t1/2(S) were found to be 50 min ± 0.001 and 6 h 30 min ± 0.005, respectively. Imaging and biodistribution studies showed a significant accumulation of 99mTc DTPA-bis(alendronate) conjugate at bone site. Bone-to-muscles ratios were 12.08 ± 0.001 at 1 h, 45.33 ± 0.001 at 4 h and 35.83 ± 0.001 at 24 h after post-injection, respectively. The receptor binding of the 99mTc- DTPA-bis (alendronate) was established on human bone cell line (Soas-2) revealed KD = 0.86 n m. The preliminary result of the 99mTc- DTPA-bis(alendronate) is encouraging to carrying out further in vivo experiment for targeted bone imaging because of good-bone-to-normal-organ contrast. Further docking analysis with molecular targets, farnesyl diphosphate synthase, geranylgeranyl pyrophosphate and osteocalcin revealed the high affinity of −17.419 and thus represents strong potential of bone-imaging agent. [ABSTRACT FROM AUTHOR]

99mTc-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 differentl-amino acids (methyl tryptophan, and 5-hydroxy tryptophan) and were characterized on the basis of IR, NMR, and Mass spectroscopy. 99mTc-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 t1/2(F) and t1/2(S) were found to be 20 ± 0.001 min for DTPA-(Me-Trp)2 and 18 ± 0.001 min for DTPA-(5HT)2 and t1/2 (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 froml-5-hydroxytryptophan exhibited remarkable localization at tumor site; whereas radiotracer derived froml-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 99mTc-DTPA-(Me trp)2 and 4.97 ± 0.001 and 5.8 ± 0.001 at 1 and 4 h after postinjection for 99mTc-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. [ABSTRACT FROM AUTHOR]