title: On the use of [18F]DOPA as an imaging biomarker for transplanted islet mass.
abstract: OBJECTIVE
  Islet transplantation is being developed as a potential cure for patients with type 1 diabetes. There is a need for non-invasive imaging techniques for the quantification of transplanted islets, as current transplantation sites are associated with a substantial loss of islet viability. The dopaminergic metabolic pathway is present in the islets; therefore, we propose Fluorine-18 labeled L-3,4-dihydroxyphenylalanine ([18F]DOPA) as a biomarker for transplanted islet mass.
  
  
  METHODS
  The expression of enzymes involved in the dopaminergic metabolic pathway was investigated in both native and transplanted human islets. The specific uptake of [18F]DOPA in islets and immortalized beta cells was studied in vitro by selective blocking of dopa decarboxylase (DDC). Initial in vivo PET imaging of viable subcutaneous human islets was performed using [18F]DOPA.
  
  
  RESULTS
  DDC and vesicular monoamine transporter 2 are co-localized with insulin in the native human pancreas, and the expression is retained after transplantation. Islet uptake of the [18F]DOPA could be modulated by inhibiting DDC, indicating that the uptake followed the normal dopaminergic metabolic pathway. In vivo imaging revealed [18F]DOPA uptake at the site of the functional islet graft.
  
  
  CONCLUSIONS
  Based on the in vitro and in vivo results presented in this study, we propose to further validate [18F]DOPA-PET as a sensitive imaging modality for imaging extrahepatically transplanted islets.
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Eriksson
authors.forename: Akiva
authors.initials: A
authors.lastname: Mintz
authors.forename: Chengyang
authors.initials: C
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
authors.forename: Abass
authors.initials: A
authors.lastname: Alavi
mesh_terms: D000818:Animals; D001692:Biological Transport; D002264:Carboxylic Acids / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050417:Insulin-Secreting Cells / Q000000981:diagnostic imaging / Q000378:metabolism; D007515:Islets of Langerhans / Q000033:anatomy & histology* / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D051379:Mice; D009929:Organ Size; D049268:Positron-Emission Tomography
chemical_list: D002264:Carboxylic Acids; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004296:Dopa Decarboxylase