PET imaging of amyloid with Florbetapir F 18 and PET imaging of dopamine degeneration with 18F-AV-133 (florbenazine) in patients with Alzheimer's disease and Lewy body disorders.
BACKGROUND
Biomarkers based on the underlying pathology of Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB) have the potential to improve diagnosis and understanding of the substrate for cognitive impairment in these disorders. The objective of this study was to compare the patterns of amyloid and dopamine PET imaging in patients with AD, DLB and Parkinson's disease (PD) using the amyloid imaging agent florbetapir F 18 and 18F-AV-133 (florbenazine), a marker for vesicular monamine type 2 transporters (VMAT2).


METHODS
Patients with DLB and AD, Parkinson's disease (PD) and healthy controls (HC) were recruited for this study. On separate days, subjects received intravenous injections of florbetapir, and florbenazine. Amyloid burden and VMAT2 density were assessed quantitatively and by binary clinical interpretation. Imaging results for both tracers were compared across the four individual diagnostic groups and for combined groups based on underlying pathology (AD/DLB vs. PD/HC for amyloid burden and PD/DLB vs. AD/HC for VMAT binding) and correlated with measures of cognition and parkinsonism.


RESULTS
11 DLB, 10 AD, 5 PD, and 5 controls participated in the study. Amyloid binding was significantly higher in the combined AD/DLB patient group (n = 21) compared to the PD/HC groups (n = 10, mean SUVr: 1.42 vs. 1.07; p = 0.0006). VMAT2 density was significantly lower in the PD/DLB group (n = 16) compared to the AD/ HC group (n = 15; 1.83 vs. 2.97; p < 0.0001). Within the DLB group, there was a significant correlation between cognitive performance and striatal florbenazine binding (r = 0.73; p = 0.011).


CONCLUSIONS
The results of this study show significant differences in both florbetapir and florbenazine imaging that are consistent with expected pathology. In addition, VMAT density correlated significantly with cognitive impairment in DLB patients (ClinicalTrials.gov identifier: NCT00857506, registered March 5, 2009).
Andrew
A
Siderowf
Michael J
MJ
Pontecorvo
Holly A
HA
Shill
Mark A
MA
Mintun
Anupa
A
Arora
Abhinay D
AD
Joshi
Ming
M
Lu
Charles H
CH
Adler
Douglas
D
Galasko
Carolyn
C
Liebsack
Daniel M
DM
Skovronsky
Banner Sun Health Research Institute, Sun City, AZ 10515W Santa Fe Dr, USA. marwan.sabbagh@bannerhealth.com.
Marwan N
MN
Sabbagh
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds / Q000009:adverse effects; D004298:Dopamine / Q000378:metabolism; D004338:Drug Combinations; D005026:Ethylene Glycols / Q000009:adverse effects; D005260:Female; D005462:Fluorine Radioisotopes / Q000009:adverse effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020961:Lewy Body Disease / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000009:adverse effects / Q000379:methods*; D019275:Radiopharmaceuticals / Q000009:adverse effects; D013747:Tetrabenazine / Q000009:adverse effects / Q000031:analogs & derivatives*
D000682:Amyloid; D000814:Aniline Compounds; D004338:Drug Combinations; D005026:Ethylene Glycols; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C545186:florbetapir; C549477:florbenazine F 18; D004298:Dopamine; D013747:Tetrabenazine