title: Striatal adenosine A(2A) receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [(18)F]-MRS5425.
abstract: BACKGROUND
  A(2A) receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an (18)F-labeled A(2A) analog radiotracer ([(18)F]-MRS5425) for A(2A) receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A(2A) receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra.
  
  
  METHODS
  [(18)F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D(2) agonist quinpirole (1.0 mg/kg) or D(2) antagonist raclopride (6.0 mg/kg).
  
  
  RESULTS
  Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres.
  
  
  CONCLUSIONS
  Thus, increase of A(2A) receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Abesh Kumar
authors.initials: AK
authors.lastname: Bhattacharjee
authors.forename: Lixin
authors.initials: L
authors.lastname: Lang
authors.forename: Orit
authors.initials: O
authors.lastname: Jacobson
authors.forename: Bidhan
authors.initials: B
authors.lastname: Shinkre
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: William C
authors.initials: WC
authors.lastname: Trenkle
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
mesh_terms: D000818:Animals; D001345:Autoradiography; D001692:Biological Transport; D007267:Injections; D008297:Male; D017072:Neostriatum / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity*; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D019257:Quinpirole / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D011854:Radiochemistry; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D014230:Triazoles / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: C568679:7-(3-(4-(2-fluoroethoxy)phenyl)propyl)-2-(furan-2-yl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidin-5-amine; D011720:Pyrazoles; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D014230:Triazoles; D019257:Quinpirole; D020891:Raclopride; D016627:Oxidopamine