| In vivo studies of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease. | |
| | |
MedLine Citation:
|
PMID: 20447560 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
INTRODUCTION: The utility of [(18)F]FPBM [2-(2'-((dimethylamino)methyl)-4'-(3-[(18)F]-fluoropropoxy)phenylthio)benzenamine], a selective serotonin transporter (SERT) tracer, and [(18)F]AV-133 [(+)-2-Hydroxy-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-1,2,3,4,6,7-hexahydro-11bH-benzo[a]quinolizine], a selective vesicular monoamine transporter 2 (VMAT2) tracer, were tested in the 6-hydroxydopamine (6-OHDA) unilateral lesioned rat model. METHODS: Positron emission tomography (PET) imaging of three 6-OHDA unilateral lesioned male Sprague Dawley rats (Rats 1-3) were performed with [(18)F]FPBM and [(18)F]AV-133 to examine whether changes in SERT and VMAT2 binding, respectively, could be detected in the brain. The brains of the three rats were then removed and examined by in vitro autoradiography with [(18)F]FPBM and the dopamine transporter ligand, [(125)I]IPT [N-(3'-[(125)I]-iodopropen-2'-yl)-2-beta-carbomethoxy-3-beta-(4-chloro phenyl) tropane, for confirmation. Biodistribution of [(18)F]FPBM in a separate group of p-chloroamphetamine (PCA) treated rats were also performed. RESULTS: PET image analysis showed varying levels of SERT binding reduction (Rat 1=-11%, Rat 2=-4%, Rat 3=-43%; n=2) and a clear and definitive loss of VMAT2 binding (Rat 1=-87%, Rat 2=-72%, and Rat 3=-91%; n=1) in the left striatum when compared to the right (non-lesioned side) striatum. The results from PET imaging were corroborated with quantitative in vitro autoradiography. Rats treated with a selective serotonin toxin (p-chloroamphetamine) showed a significant reduction of [(18)F]FPBM uptake in the cortex and hypothalamus regions of the brain. CONCLUSION: The preliminary data suggest that [(18)F]FPBM and [(18)F]AV-133 may be useful for the examination of serotonergic and dopaminergic neuron integrity, respectively, in the living brain. |
| | |
Authors:
|
Julie L Wang; Shunichi Oya; Ajit K Parhi; Brian P Lieberman; Karl Ploessl; Catherine Hou; Hank F Kung |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
|
Title: Nuclear medicine and biology Volume: 37 ISSN: 1872-9614 ISO Abbreviation: Nucl. Med. Biol. Publication Date: 2010 May |
Date Detail:
|
Created Date: 2010-05-07 Completed Date: 2010-08-17 Revised Date: 2011-07-28 |
Medline Journal Info:
|
Nlm Unique ID: 9304420 Medline TA: Nucl Med Biol Country: England |
Other Details:
|
Languages: eng Pagination: 479-86 Citation Subset: IM |
Copyright Information:
|
(c) 2010 Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aniline Compounds
/
diagnostic use,
metabolism* Animals Autoradiography Disease Models, Animal Fluorine Radioisotopes / diagnostic use* Male Parkinson Disease / drug therapy, metabolism*, radionuclide imaging Positron-Emission Tomography Protein Binding / drug effects Radioactive Tracers Rats Rats, Sprague-Dawley Serotonin Plasma Membrane Transport Proteins / metabolism* Substrate Specificity Tetrabenazine / analogs & derivatives*, diagnostic use, metabolism Vesicular Monoamine Transport Proteins / metabolism* p-Chloroamphetamine / pharmacology, therapeutic use |
| Grant Support | |
ID/Acronym/Agency:
|
R01 MH068782-05/MH/NIMH NIH HHS; R0I-MH068782/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/2-(2-((dimethylamino)methyl)-4-(3-fluoropropoxy)phenylthio)benzenamine; 0/9-fluoropropyldihydrotetrabenazine; 0/Aniline Compounds; 0/Fluorine Radioisotopes; 0/Radioactive Tracers; 0/Serotonin Plasma Membrane Transport Proteins; 0/Slc18a2 protein, rat; 0/Vesicular Monoamine Transport Proteins; 58-46-8/Tetrabenazine; 64-12-0/p-Chloroamphetamine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: In vivo evaluation of [123I]-4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(4-iodobenzyl)piperidine, an ...
Next Document: 18F-labeling and evaluation of novel MDL 100907 derivatives as potential 5-HT2A antagonists for mole...