Rj. Lederman et al., Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG), NUCL MED C, 22(7), 2001, pp. 747-753
Inflammation contributes to atherosclerotic plaque remodeling, enlargement
and rupture. Non-invasive imaging of coronary artery inflammation could hel
p target therapy to 'vulnerable' atheromata, but is limited because of smal
l tissue mass and arterial motion. Local radiopharmaceutical imaging may ov
ercome some of these limitations. We used a positron-sensitive fiberoptic p
robe, which can distinguish positron emissions from annihilation photons, t
o identify diseased from healthy endothelium in an atherosclerotic model. N
ew Zealand White rabbits underwent Fogarty-catheter injury of an iliac arte
ry and then were fed a high-fat diet for 3 weeks. Fasted animals received 9
0-180 MBq of 18-fluorodeoxyglucose (FDG) 2-4 h before sacrifice and harvest
of injured and uninjured iliacs. Arteries were incised longitudinally and
the probe was placed in contact with the arterial intima. Multiple measurem
ents were obtained along 1 cm artery segments in 60 s intervals, and correc
ted for F-18 decay and background. Measurements were recorded over 93 injur
ed and normal artery segments in 11 animals. Mean probe Z-scores were 4.8-f
old higher (CI 3.4-6.3) over injury atherosclerosis compared with uninjured
normal iliac artery segments (P < 0.001). Gamma counting confirmed that in
jured artery segments accumulated more FDG per gram than did normal segment
s (0.203%.kg injected dose per gram of tissue versus 0.042, P < 0.001). Non
-arterial tissue also accumulated FDG avidly, particularly reticuloendothel
ial tissues and blood. Delayed sacrifice, 4 h compared with 2 h after anima
l FDG injection, further reduced blood background counts and improved the s
ignal-to-noise ratio. Histopathology confirmed that injured iliac artery ha
d significantly higher intimal and medial cross-sectional area compared wit
h uninjured artery. Injured artery also had significantly higher macrophage
and smooth muscle cell density. Positron-sensitive probe counts correlated
with the intima to media ratio (r = 0.63, P = 0.03). Our positron-sensitiv
e probe distinguishes atherosclerotic from healthy artery in a blood-free f
ield. Intravascular study of plaque biology may be feasible using FDG and a
positron-sensitive probe. ((C) 2001 Lippincott Williams & Wilkins).