title: Synthesis and evaluation of Tc-99m DTPA-glutathione as a non-invasive tumor imaging agent in a mouse colon cancer model.
abstract: OBJECTIVE
  Glutathione (GSH) plays a critical role in detoxification reactions by reducing the levels of reactive oxygen species in cancer cells. This study aimed to develop technetium (Tc)-99m diethylenetriaminepentaacetic acid (DTPA)-GSH as a tumor imaging agent, and to evaluate the diagnostic performance of Tc-99m DTPA-GSH in terms of its ability to differentiate tumors from inflammatory lesions.
  
  
  METHODS
  DTPA-GSH was synthesized by reaction of GSH with DTPA anhydride under anhydrous conditions in a nitrogen atmosphere. DTPA-GSH was then reacted with Tc-99m sodium pertechnetate in a tin (II) chloride (SnCl2) solution. Gamma camera imaging was performed after intravenous injection of Tc-99m DTPA-GSH into a mouse CT-26 colon cancer model, or a mouse model of inflammation induced by the intramuscular injection of Freund's complete adjuvant.
  
  
  RESULTS
  DTPA-GSH was successfully prepared via a straightforward synthetic procedure and radiolabeled with Tc-99m at a high labeling efficiency (>95%). Tc-99m DTPA-GSH was strongly internalized by tumors in colon cancer model mice, with the tumor-to-normal muscle ratio of the complex reaching 4.3±0.9 at 4 h. By contrast, Tc-99m DTPA-GSH showed relatively weak uptake in inflammatory lesions (target-to-non-target ratio=2.0±0.3 at 4 h). A competition study showed that the uptake of Tc-99m DTPA-GSH into tumors was blocked by co-injection with high concentrations of free GSH.
  
  
  CONCLUSIONS
  The results of this work indicate that Tc-99m DTPA-GSH is a good candidate for development as a non-invasive tumor imaging agent. Furthermore, Tc-99m DTPA-GSH effectively distinguished between cancerous tissue and inflammatory lesions.
authors.affiliation: Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan, Korea.
authors.forename: Dae-Weung
authors.initials: DW
authors.lastname: Kim
authors.forename: Woo Hyoung
authors.initials: WH
authors.lastname: Kim
authors.forename: Myoung Hyoun
authors.initials: MH
authors.lastname: Kim
authors.forename: Chang Guhn
authors.initials: CG
authors.lastname: Kim
authors.forename: Chang-Sok
authors.initials: CS
authors.lastname: Oh
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Min
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D011877:Radionuclide Imaging; D016284:Technetium Tc 99m Pentetate / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D005978:Glutathione; D016284:Technetium Tc 99m Pentetate