title: Preparation and pre-vivo evaluation of no-carrier-added, carrier-added and cross-complexed [(68)Ga]-EDTMP formulations.
abstract: OBJECTIVE
  The present study aimed to develop convenient preparation and quality control protocols for [(68)Ga]-EDTMP, a potential radiotracer for skeletal PET imaging. Furthermore, bone binding characteristics with special focus on the influence of carrier addition were evaluated.
  
  
  METHODS
  No-carrier-added (nca), carrier-added and novel cross-complexed [(68)Ga]-EDTMP formulations were prepared using [(68)Ga]-gallium chloride and a commercial EDTMP kit. Respective bone binding characteristics were determined on the basis of an established in-vitro method using hydroxyapatite and human bone powders as binding matrices.
  
  
  RESULTS
  Pre-vivo evaluation of nca [(68)Ga]-EDTMP yielded irreversible binding on the mineral bone phase characterised by fast binding kinetics. Generally, nca [(68)Ga]-EDTMP showed low uptake values comparable to nca [(99m)Tc]-EDTMP. Interestingly, the bone binding affinity of [(68)Ga]-EDTMP could be increased by the addition of carriers, presumably by changing the complex structure.
  
  
  CONCLUSIONS
  This fast and reliable preparation protocol could enable small PET facilities without onsite cyclotron to perform PET bone scans. A comparison of all cross-complexed [(68)Ga]-EDTMP preparations further strengthens the recently presented "foreign carrier theory", which highlights carrier addition as a factor strongly affecting bone uptake of radiolabelled polyphosphonates. The clinical applicability of [(68)Ga]-EDTMP - particularly with respect to lesion specificity and sensitivity - should be clarified in forthcoming in-vivo studies.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Toegel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.forename: Leonhard K
authors.initials: LK
authors.lastname: Mien
authors.forename: Helmut
authors.initials: H
authors.lastname: Viernstein
authors.forename: Rainer
authors.initials: R
authors.lastname: Kluger
authors.forename: Harald
authors.initials: H
authors.lastname: Eidherr
authors.forename: Daniela
authors.initials: D
authors.lastname: Haeusler
authors.forename: Kurt
authors.initials: K
authors.lastname: Kletter
authors.forename: Robert
authors.initials: R
authors.lastname: Dudczak
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
mesh_terms: D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006801:Humans; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D005710:Gallium Radioisotopes; D009943:Organophosphorus Compounds; C018940:(ethylenedinitrilo)-tetramethylenephosphonic acid