Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent--a pilot study.
OBJECTIVE
The compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([(18)F]AV-45) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid (A beta) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [(18)F]AV-45 in human subjects.


METHODS
In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0+/-5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7+/-13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information.


RESULTS
In vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12+/-0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7+/-78.6 microGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq, respectively.


CONCLUSIONS
[(18)F]AV-45 binds specifically to A beta in vitro, and is a safe PET tracer for studying A beta distribution in human brain. The dosimetry is suitable for clinical and research application.
Lin
Kun-Ju
KJ
Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan.
Hsu
Wen-Chuin
WC
Hsiao
Ing-Tsung
IT
Wey
Shiaw-Pyng
SP
Jin
Lee-Way
LW
Skovronsky
Daniel
D
Wai
Yau-Yau
YY
Chang
Hsiu-Ping
HP
Lo
Chuan-Wei
CW
Yao
Cheng Hsiang
CH
Yen
Tzu-Chen
TC
Kung
Mei-Ping
MP
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism / Q000493:pharmacokinetics*; D052160:Benzothiazoles; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D016022:Case-Control Studies; D005026:Ethylene Glycols / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D011874:Radiometry; D013844:Thiazoles / Q000378:metabolism
D000682:Amyloid; D000814:Aniline Compounds; D052160:Benzothiazoles; D005026:Ethylene Glycols; D005456:Fluorescent Dyes; D005462:Fluorine Radioisotopes; D013844:Thiazoles; C009462:thioflavin T; C545186:florbetapir