title: Preparation of (99m)Tc carbonyl DTPA-bevacizumab and its bioevaluation in a melanoma model.
abstract: OBJECTIVE
  The objective of this study was to explore the potential of (99m)Tc carbonyl labeled DTPA-bevacizumab as a tumor imaging agent. Bevacizumab (Avastin) is a humanized monoclonal antibody (MoAb) that inhibits the vascular endothelial growth factor (VEGF).
  
  
  METHODS
  Bevacizumab was conjugated with paraisothiocyanatobenzyl diethylenetriamine pentaacetic acid (p-SCN-Bn-DTPA) and subsequently radiolabeled with (99m)Tc via the (99m)Tc carbonyl synthon. The radioconjugate after purification was characterized by SE-HPLC and its in vitro stability was determined by histidine challenge experiments. Biodistribution studies to determine the uptake by tumors were carried out in melanoma model.
  
  
  RESULTS
  The radiochemical purity of (99m)Tc carbonyl labeled antibody was >98 %. The radiolabeled antibody exhibited good stability in the histidine challenge experiments up to 24 h when stored at 37 °C. Biodistribution studies in mice bearing melanoma showed significant tumor uptake (6.9 ± 2.2 % ID/g at 24 h p.i.) which was reduced to 1.6 ± 0.4 % ID/g on co-injection with cold Bevacizumab.
  
  
  CONCLUSIONS
  The (99m)Tc carbonyl-DTPA-bevacizumab conjugate with good radiochemical purity, excellent stability and good specificity for VEGF indicates its potential as a radioimmunoscintigraphy agent for various cancers.
authors.affiliation: Radiopharmaceutical Evaluation Section, Isotope Applications and Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
authors.forename: Mythili
authors.initials: M
authors.lastname: Kameswaran
authors.forename: Usha
authors.initials: U
authors.lastname: Pandey
authors.forename: Haladhar Dev
authors.initials: HD
authors.lastname: Sarma
authors.forename: Grace
authors.initials: G
authors.lastname: Samuel
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008545:Melanoma / Q000000981:diagnostic imaging*; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D013667:Technetium / Q000493:pharmacokinetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D000068258:Bevacizumab; D006639:Histidine; D013667:Technetium; D004369:Pentetic Acid