title: A rapid solid-phase extraction method for measurement of non-metabolised peripheral benzodiazepine receptor ligands, [(18)F]PBR102 and [(18)F]PBR111, in rat and primate plasma.
abstract: OBJECTIVE
  To develop a rapid and reliable method for estimating non-metabolised PBR ligands fluoroethoxy ([(18)F]PBR102)- and fluoropropoxy ([(18)F]PBR111)-substituted 2-(6-chloro-2-phenyl)imidazo[1,2-a]pyridine-3-yl)-N,N-diethylacetamides in plasma.
  
  
  METHODS
  Rats and baboons were imaged with PET up to 2 h postinjection of [(18)F]PBR102 and [(18)F]PBR111 under baseline conditions, after pre-blocking or displacement with PK11195. Arterial plasma samples were directly analysed by reverse-phase solid-phase extraction (RP-SPE) and RP-HPLC and by normal-phase TLC. SPE cartridges were successively washed with acetonitrile/water mixtures. SPE eluant radioactivity was measured in a γ-counter to determine the parent compound fraction and then analysed by HPLC and TLC for validation.
  
  
  RESULTS
  In SPE, hydrophilic and lipophilic radiolabelled metabolites were eluted in water and 20% acetonitrile/water. All non-metabolised [(18)F]PBR102 and [(18)F]PBR111 were in SPE acetonitrile fraction as confirmed by HPLC and TLC analysis. Unchanged (%) [(18)F]PBR102 and [(18)F]PBR111 from SPE analysis in rat and baboon plasma agreed with those from HPLC and TLC analysis. In rats and baboons, the fraction of unchanged tracer followed a bi-exponential decrease, with half-lives of 7 to 10 min for the fast component and >80 min for the slow component for both tracers.
  
  
  CONCLUSIONS
  Direct plasma SPE analysis of [(18)F]PBR102 and [(18)F]PBR111 can reliably estimate parent compound fraction. SPE was superior to HPLC for samples with low activity; it allows rapid and accurate metabolite analysis of a large number of plasma samples for improved estimation of metabolite-corrected input function during quantitative PET imaging studies.
authors.affiliation: ANSTO LifeSciences, Sydney 2234, Australia. andrew.katsifis@ansto.gov.au
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
authors.forename: Christian
authors.initials: C
authors.lastname: Loc'h
authors.forename: David
authors.initials: D
authors.lastname: Henderson
authors.forename: Thomas
authors.initials: T
authors.lastname: Bourdier
authors.forename: Tien
authors.initials: T
authors.lastname: Pham
authors.forename: Ivan
authors.initials: I
authors.lastname: Greguric
authors.forename: Peter
authors.initials: P
authors.lastname: Lam
authors.forename: Paul
authors.initials: P
authors.lastname: Callaghan
authors.forename: Filomena
authors.initials: F
authors.lastname: Mattner
authors.forename: Stefan
authors.initials: S
authors.lastname: Eberl
authors.forename: Michael
authors.initials: M
authors.lastname: Fulham
mesh_terms: D000081:Acetamides / Q000097:blood* / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods*; D002352:Carrier Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D008024:Ligands; D008297:Male; D010215:Papio; D019275:Radiopharmaceuticals / Q000097:blood / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000379:methods*; D013997:Time Factors
chemical_list: D000081:Acetamides; D002352:Carrier Proteins; D005462:Fluorine Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; C069997:Tspo protein, rat