Quantitative in vitro phosphor imaging using [3H] and [18F] radioligands: the effects of chronic desipramine treatment on serotonin 5-HT2 receptors.
Traditionally, autoradiography of neuroreceptors is performed in vitro using tritiated ligands and low sensitivity X-ray film, requiring long exposure times. In vivo imaging of neuroreceptors using positron emission tomography (PET) suffers poor spatial resolution, but in vitro PET autoradiography is difficult with film due to the short half-life of the isotopes. Storage phosphor screens provide an extremely sensitive alternative to film. To demonstrate and validate quantitative in vitro phosphor imaging with PET and tritiated ligands, we treated rats chronically with the antidepressant desipramine, which results in decreased binding to serotonin 5-HT(2) receptors. Serotonin 5-HT(2) binding decreased significantly in all cortical regions examined as measured by both [(3)H]ketanserin and [(18)F]setoperone. The data from the two radioligands were not significantly different, and the distribution of the receptors was in agreement with previous reports. We also present data on the reusability of tritium-sensitive phosphor screens, and show that the use of simple corrections allows receptor binding data with PET ligands to be compared across different days. The results indicate that phosphor imaging is a valid, fast, and quantifiable technique for measuring neuroreceptor regulation, and that it provides an excellent tool to corroborate in vivo PET data in vitro at higher resolution.
Strome
Elissa M
EM
Pacific Parkinson's Research Centre and UBC/TRIUMF PET Group, University of British Columbia, Purdy Pavilion M36,2221 Wesbrook Mall, Vancouver, B.C., Canada V6T 2B5. strome@interchange.ubc.ca
Jivan
Salma
S
Doudet
Doris J
DJ
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001345:Autoradiography / Q000295:instrumentation / Q000379:methods*; D001667:Binding, Competitive / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003891:Desipramine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005462:Fluorine Radioisotopes / Q000378:metabolism; D008024:Ligands; D008163:Luminescent Measurements / Q000295:instrumentation / Q000379:methods*; D008297:Male; D009480:Neuropharmacology / Q000295:instrumentation / Q000379:methods; D011869:Radioligand Assay / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044348:Receptors, Serotonin, 5-HT2 / Q000032:analysis* / Q000187:drug effects; D014316:Tritium / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D005462:Fluorine Radioisotopes; D008024:Ligands; D044348:Receptors, Serotonin, 5-HT2; D014316:Tritium; D003891:Desipramine