title: 99mTc-labeling of colchicine using [99mTc(CO)3(H2O)3]+ and [99mTc triple bond N]2+ core for the preparation of potential tumor-targeting agents.
abstract: Multidrug resistance (MDR) mediated by over-expression of P-glycoprotein (Pgp) is one of the major causes of failure of chemotherapy in cancer treatment. Colchicine, a naturally occurring alkaloid, is a Pgp substrate and acts as an antimitotic agent by binding to microtubules. Hence, Colchicine and its analogues radiolabeled with 99mTc may have potential for visualization of MDR in tumors. Here we report 99mTc-labeling of colchicine derivatives using [99mTc(CO)3(H2O)3]+ and [99mTc triple bond N]2+ cores. Trimethylcolchicinic acid synthesized from colchicine was used as the precursor to prepare iminodiacetic acid and dithiocarbamate derivatives which were then radiolabeled with [99mTc(CO)3(H2O)3]+ and [99mTc triple bond N]2+ cores, respectively. Radiolabeling yield for both the complexes was > 98% as observed by HPLC and TLC patterns. In vitro studies in tumor cell lines showed significant uptake for 99mTc-carbonyl as well as for 99mTc-nitrido colchicine complexes. Biodistribution studies in Swiss mice bearing fibrosarcoma tumor showed 4.1 +/- 1.2% ID/g of uptake at 30 min pi for 99mTc(CO)3-complex as against 0.42 +/- 0.24% ID/g for the 99mTcN-complex. 99mTc(CO)3-colchicine complex exhibited better pharmacokinetics with lower liver accumulation as compared to the 99mTcN-complex. Thus, colchicine radiolabeled with [99mTc(CO)3(H2O)3]+ core is more promising with respect to in vivo distribution characteristics in tumor model.
authors.affiliation: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
authors.forename: Aruna
authors.initials: A
authors.lastname: Korde
authors.forename: Drishty
authors.initials: D
authors.lastname: Satpati
authors.forename: Anupam
authors.initials: A
authors.lastname: Mathur
authors.forename: Madhava
authors.initials: M
authors.lastname: Mallia
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
authors.forename: Kanchan
authors.initials: K
authors.lastname: Kothari
authors.forename: H D
authors.initials: HD
authors.lastname: Sarma
authors.forename: Pradeep
authors.initials: P
authors.lastname: Choudhari
authors.forename: Meera
authors.initials: M
authors.lastname: Venkatesh
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005354:Fibrosarcoma / Q000000981:diagnostic imaging; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging; D051379:Mice; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D003078:Colchicine