In vivo measurement of vesicular monoamine transporter type 2 density in Parkinson disease with (18)F-AV-133.
PET provides a noninvasive means to evaluate the functional integrity of the presynaptic monoaminergic system in the living human brain.


METHODS
In this study, a novel (18)F-labeled tetrabenazine derivative, (18)F-(+)fluoropropyldihydrotetrabenazine ((18)F-AV-133), was used for the noninvasive assessment of the vesicular monoamine transporters type 2 (VMAT2) in 17 Parkinson disease (PD) patients and 6 healthy controls. The binding potential (BP) of (18)F-AV-133 was calculated using Logan graphical analysis. Voxel-based and volume-of-interest-based analyses of BP images were performed to examine brain regional reductions in VMAT2 density in PD.


RESULTS
VMAT2 BP was decreased by 81% in the posterior putamen, 70% in the anterior putamen, and 48% in the caudate nucleus of PD patients. Voxel-based analysis demonstrated VMAT2 reductions in the striatum and mid brain of PD patients. Furthermore, VMAT2 BPs in the caudate nuclei significantly correlated with the clinical severity of PD.


CONCLUSIONS
These findings indicate that the novel (18)F-labeled ligand (18)F-AV-133 can sensitively detect monoaminergic terminal reductions in PD patients. Studies with (18)F-AV-133 may allow the presymptomatic identification of individuals with disorders characterized by degeneration of dopaminergic nigrostriatal afferents.
Okamura
Nobuyuki
N
Department of Nuclear Medicine and Centre for PET, Austin Health, Victoria, Australia.
Villemagne
Victor L
VL
Drago
John
J
Pejoska
Svetlana
S
Dhamija
Rajinder K
RK
Mulligan
Rachel S
RS
Ellis
Julia R
JR
Ackermann
Uwe
U
O'Keefe
Graeme
G
Jones
Gareth
G
Kung
Hank F
HF
Pontecorvo
Michael J
MJ
Skovronsky
Daniel
D
Rowe
Christopher C
CC
D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D019275:Radiopharmaceuticals; D013747:Tetrabenazine / Q000031:analogs & derivatives; D014018:Tissue Distribution; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; D013747:Tetrabenazine