title: 18F-Fallypride PET of pancreatic islets: in vitro and in vivo rodent studies.
abstract: Islet cell loss in the pancreas results in diabetes. A noninvasive method that measures islet cell loss and also tracks the fate of transplanted islets would facilitate the development of novel therapeutics and improve the management of diabetes. We describe a novel dopamine D(2)/D(3) receptor (D(2)/D(3)R)-based PET method to study islet cells in the rat pancreas and in islet cell transplantation.
  
  
  METHODS
  (18)F-fallypride binding to isolated rat islets and pancreas was evaluated in the absence and presence of the D(2)/D(3)R inhibitor haloperidol. After intravenous (18)F-fallypride (28-37 MBq) administration, normal rats and rats pretreated with haloperidol were imaged in a PET/CT scanner and subsequently studied ex vivo for (18)F-fallypride localization in the pancreas. A streptozotocin-treated diabetic rat model was used to study localization of (18)F-fallypride in the pancreas, in vitro and ex vivo. Rat islet cells were transplanted into the spleen and visualized using (18)F-fallypride PET.
  
  
  RESULTS
  (18)F-fallypride bound to isolated islet cells and pancreatic sections with an endocrine or exocrine selectivity of approximately 4; selectivity was reduced by haloperidol, suggesting that binding was D(2)/D(3)R-specific. Chemical destruction of islets by streptozotocin decreased (18)F-fallypride binding in pancreas by greater than 50%, paralleling the decrease in insulin immunostaining. Uptake of (18)F-fallypride in the pancreas was confirmed by radiochromatography and was 0.05% injected dose/cm(3) as measured by PET/CT. The ratio of (18)F-fallypride uptake in the pancreas to reference tissue (erector spinae muscle) was 5.5. Rat islets transplanted into the spleen were visualized in vivo by (18)F-fallypride and confirmed by immunostaining. The ratio of spleen-transplanted islets to erector spinae muscle was greater than 5, compared with a ratio of 2.8 in untransplanted rats.
  
  
  CONCLUSIONS
  These studies demonstrate the potential utility of (18)F-fallypride as a PET agent for islet cells.
authors.affiliation: Preclinical Imaging Center, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California 92697, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Garcia
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Mirbolooki
authors.forename: Cristian
authors.initials: C
authors.lastname: Constantinescu
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Pan
authors.forename: Evegueni
authors.initials: E
authors.lastname: Sevrioukov
authors.forename: Norah
authors.initials: N
authors.lastname: Milne
authors.forename: Ping H
authors.initials: PH
authors.lastname: Wang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lakey
authors.forename: K George
authors.initials: KG
authors.lastname: Chandy
authors.forename: Jogeshwar
authors.initials: J
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D001549:Benzamides / Q000378:metabolism; D001692:Biological Transport; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging; D005240:Feasibility Studies; D007515:Islets of Langerhans / Q000000981:diagnostic imaging* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000000981:diagnostic imaging; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011759:Pyrrolidines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000637:transplantation; D014057:Tomography, X-Ray Computed
chemical_list: D001549:Benzamides; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines