当前位置： SCI文献检索 > NUCLEAR MEDICINE AND BIOLOGY期刊下所有文献 > In vivo studies of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease.

In vivo studies of the SERT-selective [18F]FPBM and VMAT2-selective [18F]AV-133 radiotracers in a rat model of Parkinson's disease.

Abstract：

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.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Wang JL,Oya S,Parhi AK,Lieberman BP,Ploessl K,Hou C,Kung HF

doi

10.1016/j.nucmedbio.2010.01.006

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

479-86

issue

4

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(10)00028-4

journal_volume

37

pub_type

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