title: Lessons from 11C-dihydrotetrabenazine imaging in a xenograft mouse model of rat insulinoma: is PET imaging of pancreatic beta cell mass feasible?
abstract: BACKGROUND
  The feasibility of beta cell mass (BCM) imaging and quantification with positron emission tomography (PET) in the pancreas is controversial. In an effort to shed some light on this topic, we have used a xenograft model of rat insulinoma (RIN) in mice, mimicking an intramuscular islet transplantation situation.
  
  
  METHODS
  A total of 105 RIN cells were subcutaneously implanted in nude mice (N.=8). Tumor size and glycaemia levels were determined daily. Rat C-peptide was measured to demonstrate rat insulin production. PET imaging with 11C-(+)-α-dihydrotetrabenazine (11C-DTBZ) was done at 3 and 4 weeks and compared with 18F-FDG and 18F-DOPA studies in the same mice. Ex-vivo autoradiography with 11C-DTBZ was carried out in frozen sections of tumors. VMAT2 expression was measured by Western-blot and immunohistochemistry in tumors and RIN cells.
  
  
  RESULTS
  Functional rat insulin production in mice was demonstrated by substantial decrease in glycaemia (<50 mg/dL by week 4) and rat C-peptide levels (7.2±2.6 ng/mL) similar to those measured in control rats. PET studies showed that tumor imaging with 11C-DTBZ at four (N.=8) and five (N.=5) weeks was negative; only bigger tumors could be seen with 18F-DOPA. In explanted tumors 11C-DTBZ autoradiography was negative, albeit VMAT2 expression measured by Western-blot and immunohistochemistry was lower than in cultured RIN cells.
  
  
  CONCLUSIONS
  Although insulinomas are fully functional it does not seem feasible to use 11C-DTBZ for in-vivo measuring of BCM. This might either be due to inherent technical limitations of PET, decrease in VMAT2 expression in the tumors due to unknown reasons, or other biological limiting facts.
authors.affiliation: Department of Nuclear Medicine, University of Navarra, Pamplona, Spain - mcollant@unav.es.
authors.forename: María
authors.initials: M
authors.lastname: Collantes
authors.affiliation: Hematology-Oncology Research Unit, Foundation for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.|Cell Therapy Research Unit, Foundation for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Barajas
authors.affiliation: Department of Nuclear Medicine, University of Navarra, Pamplona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Quincoces
authors.affiliation: Department of Nuclear Medicine, University of Navarra, Pamplona, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Ramos-Membrive
authors.affiliation: Department of Nuclear Medicine, University of Navarra, Pamplona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Martí-Climent
authors.affiliation: Small Animal Imaging Research Unit, Foundation for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Ecay
authors.affiliation: Cell Therapy Research Unit, Foundation for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Saray
authors.initials: S
authors.lastname: Rodríguez
authors.affiliation: Department of Endocrinology, University of Navarra, Pamplona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Escalada
authors.affiliation: Department of Nuclear Medicine, University of Navarra, Pamplona, Spain.|Cell Therapy Research Unit, Foundation for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Peñuelas
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D064593:Heterografts; D007340:Insulinoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000737:chemistry; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D050493:Vesicular Monoamine Transport Proteins; D019788:Fluorodeoxyglucose F18; C032811:dihydrotetrabenazine; D013747:Tetrabenazine