title: In vivo SPECT imaging with 111In-DOTA-c(RGDfK) to detect early pancreatic cancer in a hamster pancreatic carcinogenesis model.
abstract: Early detection of pancreatic cancer is key to overcoming its poor prognosis. α(v)β(3)-integrin is often overexpressed in pancreatic tumor cells, whereas it is scarcely expressed in normal pancreatic cells. In this study, we investigated the usefulness of SPECT imaging with (111)In-1,4,7,10-tetraazacylododecane-N,N',N″,N'''-tetraacetic acid-cyclo-(Arg-Gly-Asp-d-Phe-Lys) [(111)In-DOTA-c(RGDfK)], an imaging probe of α(v)β(3)-integrin, for the early detection of pancreatic cancer in a hamster pancreatic carcinogenesis model.
  
  
  METHODS
  Hamsters were subcutaneously injected with the pancreatic duct carcinogen N-nitrosobis(2-oxopropyl)amine to induce pancreatic cancer. N-nitrosobis(2-oxopropyl)amine-treated hamsters underwent in vivo SPECT with (111)In-DOTA-c(RGDfK). After imaging, the tumor-to-normal pancreatic tissue radioactivity ratios in excised pancreatic samples were measured with autoradiography (ARG) and compared with the immunopathologic findings for α(v)β(3)-integrin. In a mouse model in which inflammation was induced with turpentine, the uptake of (111)In-DOTA-c(RGDfK) in inflammatory regions was evaluated with ARG and compared with that of (18)F-FDG.
  
  
  RESULTS
  (111)In-DOTA-c(RGDfK) was clearly visualized in pancreatic cancer lesions as small as 3 mm in diameter. ARG analysis revealed high tumor-to-normal pancreatic tissue radioactivity ratios (4.6 ± 1.0 [mean ± SD] in adenocarcinoma and 3.3 ± 1.4 in atypical hyperplasia). The uptake of (111)In-DOTA-c(RGDfK) strongly correlated with α(v)β(3)-integrin expression. In the inflammatory model, inflammation-to-muscle ratios for (18)F-FDG and (111)In-DOTA-c(RGDfK) were 8.37 ± 4.37 and 1.98 ± 0.60, respectively. These results imply that (111)In-DOTA-c(RGDfK) has a lower rate of false-positive tumor detection than (18)F-FDG.
  
  
  CONCLUSIONS
  Our findings suggest that SPECT with (111)In-DOTA-c(RGDfK) has great potential for the early and accurate detection of pancreatic cancer.
authors.affiliation: Cancer Prevention Basic Research Project, National Cancer Center Research Institute, Tokyo, Japan. miyoshim@ncc.go.jp
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Michihiro
authors.initials: M
authors.lastname: Mutoh
authors.forename: Toshio
authors.initials: T
authors.lastname: Imai
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tsuda
authors.forename: Sadaaki
authors.initials: S
authors.lastname: Kimura
authors.forename: Izumi O
authors.initials: IO
authors.lastname: Umeda
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
authors.forename: Keiji
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D000818:Animals; D001345:Autoradiography; D006224:Cricetinae; D004195:Disease Models, Animal; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D019788:Fluorodeoxyglucose F18; D007249:Inflammation / Q000000981:diagnostic imaging; D051379:Mice; D009602:Nitrosamines / Q000633:toxicity; D009942:Organometallic Compounds; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D010456:Peptides, Cyclic; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C532506:111In-DOTA-cyclo(arginyl-glycyl-aspartyl-phenylalanyl-lysyl); D009602:Nitrosamines; D009942:Organometallic Compounds; D010456:Peptides, Cyclic; D019788:Fluorodeoxyglucose F18; C013622:nitrosobis(2-oxopropyl)amine