title: Long-term reproducibility of in vivo measures of specific binding of radioligands in rat brain.
abstract: The long-term reproducibility of measures of in vivo specific binding of radiolabeled forms of (+)-alpha-dihydrotetrabenazine (DTBZ) and d-threo-methylphenidate (MPH) in rat brain was examined. All studies were done using a consistent bolus plus infusion protocol and calculation of equilibrium distribution volume ratios (DVR). Over a period of eight years striatal DVR values for DTBZ binding to the vesicular monoamine transporter 2 (VMAT2) in young adult (8-10 wks old) rats showed very good reproducibility (3.62+/-0.33, N=35). Equivalent values were obtained using either tritiated or carbon-11 labeled DTBZ, and were irrespective of sex of animals. Older animals (78 wks old) showed losses (-45%) of specific binding. Striatal binding of MPH to the dopamine transporter (DAT) showed a similar reproducibility over a five year period (DVR=2.17+/-0.39, N=52), again irrespective of radionuclide or sex. These studies demonstrate that use of a consistent in vivo technique can provide reliable measures of specific binding of radioligands to high affinity sites in the rat brain.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. mkilbour@umich.edu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kilbourn
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008774:Methylphenidate / Q000493:pharmacokinetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012737:Sex Factors; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
chemical_list: D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; C493454:Slc18a2 protein, rat; C493216:Slc6a3 protein, rat; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D014316:Tritium; D008774:Methylphenidate; C032811:dihydrotetrabenazine; D013747:Tetrabenazine