title: Preclinical evaluation of a 68Ga-labeled biotin analogue for applications in islet transplantation.
abstract: BACKGROUND
  Islet transplantation is a promising treatment for type 1 diabetes mellitus, but the fate of the cells after intraportal infusion is unclear. It is therefore imperative to develop novel techniques for noninvasive imaging and quantification of events following islet transplantation.
  
  
  METHODS
  Small islet-like microbeads, avidin-covered agarose resins (AARs), were used as a model system for islet transplantation. Capability for specific [(68)Ga]Ga-DOTA-(PEG)(2)-biotin uptake and retention for either AARs or human islets conjugated with avidin by means of a heparin scaffold was studied in vitro. Biodistribution of the novel positron emission tomography (PET) tracer [(68)Ga]Ga-DOTA-(PEG)(2)-biotin was evaluated in mice treated by intraportal transplantation of AARs by μPET/computed tomography and ex vivo organ distribution and compared with control mice.
  
  
  RESULTS
  AARs had high capability to bind [(68)Ga]Ga-DOTA-(PEG)(2)-biotin, close to 50% of administrated tracer/μl in vitro (>0.25 MBq/μl). Avidin-tagged human islets could bind on average 2.2% of administered tracer/μl. Specificity (>90%) and retention (>90% after 1 h) were high for both AARs and avidin-tagged islets. Hepatic tracer uptake and retention were increased in mice transplanted with AARs [standardized uptake value (SUV)=2.6] compared to the untreated group (SUV=1.4). In vivo uptake of tracer to AARs was blocked by preadministration of unlabeled biotin.
  
  
  CONCLUSIONS
  Avidin-tagged islet-like objects can be tracked in hepatic volume after intraportal transplantation by using [(68)Ga]Ga-DOTA-(PEG)(2)-biotin and PET.
authors.affiliation: Platform for Preclinical PET, Department of Medicinal Chemistry, Uppsala University, SE-75187 Uppsala, Sweden. olof.eriksson@pet.medchem.uu.se
authors.forename: Olof
authors.initials: O
authors.lastname: Eriksson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Carlsson
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Blom
authors.forename: Anders
authors.initials: A
authors.lastname: Sundin
authors.forename: Bengt
authors.initials: B
authors.lastname: Långström
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.forename: Irina
authors.initials: I
authors.lastname: Velikyan
mesh_terms: D000818:Animals; D001360:Avidin / Q000737:chemistry / Q000378:metabolism; D001667:Binding, Competitive; D001710:Biotin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D005710:Gallium Radioisotopes / Q000737:chemistry; D006801:Humans; D007275:Injections, Intravenous; D007515:Islets of Langerhans / Q000000981:diagnostic imaging* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D012685:Sepharose / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D005710:Gallium Radioisotopes; D009942:Organometallic Compounds; C066402:avidin-agarose; D001360:Avidin; D001710:Biotin; D012685:Sepharose