Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG)

Abstract

Inflammation contributes to atherosclerotic plaque remodeling, enlargement and rupture. Non-invasive imaging of coronary artery inflammation could help target therapy to 'vulnerable' atheromata, but is limited because of small tissue mass and arterial motion. Local radiopharmaceutical imaging may overcome some of these limitations. We used a positron-sensitive fiberoptic probe, which can distinguish positron emissions from annihilation photons, to identify diseased from healthy endothelium in an atherosclerotic model. New Zealand White rabbits underwent Fogarty-catheter injury of an iliac artery and then were fed a high-fat diet for 3 weeks. Fasted animals received 90-180 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 measurements were obtained along 1 cm artery segments in 60 s intervals, and corrected for 18F decay and background. Measurements were recorded over 93 injured and normal artery segments in 11 animals. Mean probe Z-scores were 4.8-fold higher (CI 3.4-6.3) over injury atherosclerosis compared with uninjured normal iliac artery segments (P<0.001). Gamma counting confirmed that injured artery segments accumulated more FDG per gram than did normal segments (0.203% x kg injected dose per gram of tissue versus 0.042, P<0.001). Non-arterial tissue also accumulated FDG avidly, particularly reticuloendothelial tissues and blood. Delayed sacrifice, 4 h compared with 2 h after animal FDG injection, further reduced blood background counts and improved the signal-to-noise ratio. Histopathology confirmed that injured iliac artery had significantly higher intimal and medial cross-sectional area compared with 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-sensitive probe distinguishes atherosclerotic from healthy artery in a blood-free field. Intravascular study of plaque biology may be feasible using FDG and a positron-sensitive probe.

Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with 18F positron emission tomography

“…Hypoxia is a prominent feature of the atherosclerotic milieu and associates strongly with the burden of macrophage infiltration and inflammation (41). Animal (42)(43)(44)(45)(46)(47)(48) and human (33,(49)(50)(51) studies have consistently demonstrated a correlation between 18 F-FDG uptake and the presence and density of macrophages in atherosclerosis. 18 F-FDG PET vascular imaging in humans was first described in 1999 in Takayasu's arteritis, before being investigated in other vasculitides (52)(53)(54).…”

Comparison of 99mTc-annexin A5 with 18F-FDG for the detection of atherosclerosis in ApoE−/− mice

“…Because the metabolic and apoptotic signals are large, it is likely that even small lesions will be visible [18]. For these reasons, Tc-labeled annexin A5, a SPECT tracer as a marker of ongoing apoptotic cell death, and 18 F-FDG, a PET tracer as a marker of inflammation, are being evaluated for detecting vulnerable atherosclerotic plaques [18][19][20][21][22][23]. It…”

Detection of inflamed atherosclerotic lesions with diadenosine-5′,5‴- P 1 , P 4 -tetraphosphate (Ap 4 A) and positron-emission tomography

“…More recently, the F(abЈ) fragments of monoclonal IgM antibody Z2D3, which was initially developed with specificity for an antigen expressed by proliferating SMCs of human atherosclerotic lesions, have demonstrated rapid accumulation and good localization of lesions in an experimental atherosclerotic model (28 -29). Fluorine-18-labeled fluorodeoxyglucose has also been used for imaging of carotid artery plaque (30)(31).…”