title: Synthesis and evaluation of 99mTc(CO)(3)-DTPA-folate as a folate-receptor-targeted radiopharmaceutical.
abstract: A folate-receptor-targeted 99mTc-radiopharmaceutical, [99mTc]Tc(CO)(3)DTPA-folate, was prepared by heating [99mTc]Tc(CO)(3)(H(2)O)(3)(+) in an aqueous solution of the previously reported DTPA-folate conjugate. The radiotracer was HPLC purified (> 98% radiochemical purity) and evaluated in vitro and in vivo as an agent for targeting folate-receptor-positive cells. [99mTc]Tc(CO)(3)DTPA-folate experienced high, folate-receptor-specific uptake in human KB tumor cells. Intravenous administration of [99mTc]Tc(CO)(3)DTPA-folate to athymic mice bearing KB cell tumor xenografts resulted in 99mTc tumor uptake of 1.8 +/- 0.5 and 3.3 +/- 0.2%ID/g (n = 3) at 30 minutes and 4 hours post-injection, respectively. Tumor uptake was reduced when folic acid was co-administered with the intravenous [99mTc]Tc(CO)(3)DTPA-folate, consistent with radiopharmaceutical localization being mediated by the folate receptor.
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Trump
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Mathias
authors.forename: Zhenfan
authors.initials: Z
authors.lastname: Yang
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
authors.forename: Mary
authors.initials: M
authors.lastname: Marmion
authors.forename: Mark A
authors.initials: MA
authors.lastname: Green
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007624:KB Cells / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011869:Radioligand Assay / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011956:Receptors, Cell Surface; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011956:Receptors, Cell Surface; C470855:technetium Tc 99m tricarbonyl DTPA-folate; D005492:Folic Acid