title: Radiosynthesis and biological evaluation of 68Ga-labeled colchicine conjugates.
abstract: OBJECTIVE
  Colchicine, a plant-derived alkaloid, is a known substrate for P-glycoprotein (Pgp), which confers multidrug resistance (MDR) to cancer cells and tumors, through enhanced efflux of chemotherapeutic drugs. Hence, radiolabeled colchicine can be a suitable probe for imaging of activity of Pgp transport in vivo and early diagnosis of MDR.
  
  
  METHODS
  In the present study, colchicine was hydrolyzed to desacetylcolchiceine for conjugation with p-SCN-Bn-DOTA and p-SCN-Bn-NOTA. The resulting conjugates, DOTA-desacetylcolchiceine and NOTA-desacetylcolchiceine, were radiolabeled with 68Ga. The radiotracers 68Ga-DOTA-desacetylcolchiceine (68Ga-1) and 68Ga-NOTA-desacetylcolchiceine (68Ga-2) were evaluated in vitro (MCF-7 and T47D breast cancer cell lines) and in vivo (biodistribution studies, Swiss mice bearing fibrosarcoma tumors).
  
  
  RESULTS
  The radiotracers prepared in >97% radiochemical yield showed good in vitro binding and significant inhibition with 100-fold cold colchicine (p<0.05). In vivo the tumor uptake reached maximum at 120 minutes postinjection (68Ga-1: 2.35%±0.39% injected dose per gram [ID/g]; 68Ga-2: 1.5%±0.31% ID/g). Of the two radiotracers 68Ga-2 cleared faster from blood (p<0.05) with lower uptake in nontargeted organs as compared with 68Ga-1.
  
  
  CONCLUSIONS
  The radiotracer 68Ga-2 has shown improved pharmacokinetic features over 68Ga-1 and the previously reported 99mTc(CO)3-colchicine radiotracer. The preliminary studies with 68Ga-2 indicate its potential for in vivo targeting of tumor. However, the efficacy of the radiotracer for imaging of multidrug-resistant states will be ascertained in future.
authors: 1 Isotope Applications & Radiopharmaceuticals Division, Bhabha Atomic Research Center , Mumbai, India .
authors: Drishty
authors: D
authors: Satpati
authors: Aruna
authors: A
authors: Korde
authors: Haladhar Deb
authors: HD
authors: Sarma
authors: Sharmila
authors: S
authors: Banerjee
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D045744:Cell Line, Tumor; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D005260:Female; D005354:Fibrosarcoma / Q000000981:diagnostic imaging / Q000378:metabolism; D005710:Gallium Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D005710:Gallium Radioisotopes; D019275:Radiopharmaceuticals; D003078:Colchicine
keywords: 68Ga; DOTA; NOTA; colchicine; tumor