18F-FDG for imaging microvascular injury

Abstract

Atherosclerosis is an inflammatory process where oxidation of low-density lipoproteins (LDL) in the arterial wall causes initiation and progression of the atherosclerotic plaque by attracting macrophages. 1 The necrotic core of the vulnerable atherosclerotic plaque is rich in free cholesterol crystals derived from apoptotic lipid-laden macrophages and from the membranes of red blood cells which enter the core during intraplaque hemorrhage. 2 Vulnerable plaque is more prone to rupture. The plaque rupture triggers macrophage activation, tissue factor release, platelet aggregation, thrombus formation, thromboembolization, cholesterol embolization, arterial obstruction, end organ ischemia and necrosis. Atherosclerosis is a dynamic process and many of its clinical manifestations such as myocardial infarction, ischemic stroke, transient ischemic attack, acute mesenteric ischemia, acute limb ischemia, and renal injury occur as a consequence of rupture of the vulnerable atherosclerotic plaque. So it is very important to understand the various mechanisms behind the distal organ injury caused by acute plaque rupture.Cholesterol crystal embolization (CCE) is one known mechanism of organ injury from atherosclerotic plaque rupture and it may happen spontaneously or by the endothelial trauma during instrumentation of an artery. 3 The prevalence of cholesterol crystal embolism in autopsy studies in unselected patients ranges from 0.7% to 4%. 4 This has also been shown to occur spontaneously in 1% of patients with transesophageal echocardiography-confirmed extensive thoracic aortic athersosclerotic disease when followed over 3 years. 5 CCE occurs in 3% of patients who underwent infrarenal aortic and infrainguinal vascular surgery or angiographic manipulation, 6 in 0.8% of patients undergoing cardiac catheterization, 7 and in 0.2% of patients undergoing cardiac surgery. 8 CCE causes organ injury by multiple mechanisms. In this issue of the Journal of Nuclear Cardiology, Pervaiz MH et al 9 examine the nonobstructive, non-ischemic, direct toxicity of cholesterol crystals as a cause of left thigh muscle inflammation and injury in a controlled animal study after injecting cholesterol crystals, polystyrene microsphere control, or saline control into the left femoral artery of rabbits. Thigh muscle inflammation and injury was assessed by 18 F-FDG PET/CT and angiography, which were then correlated with inflammatory markers such as tissue macrophage infiltration density and muscle injury markers such as creatine phosphokinase (CPK) levels. There was more muscle inflammation and injury in the cholesterol crystal group compared to the control groups as demonstrated by high maximum standardized uptake values of the left thigh muscles by PET/CT (0.40 ± 0.16 vs 0.21 ± 0.11 and 0.23 ± 0.06; P = .038 and P = .036, respectively), high CPK levels at 24 hours (7.46 ± 4.32 vs 1.57 ± 0.84 and 1.43 ± 0.57; P = .007 and P = .023, respectively), and high macrophage density in the muscle biopsy.CCE may cause organ injury by multiple mechanisms such as ...

Molecular imaging of tumor-specific markers and their expression in other organs

“…Nuclear imaging provides us with a unique ability to study various biochemical, metabolic and molecular processes, expression of cell membrane proteins and receptors, matrix composition, and gene expression, at a cellular, tissue and organ level in intact animals and humans under various physiological conditions. [1][2][3][4][5][6] This involves an identification of a target inside the body, which is highly specific for a particular disease process and is abundantly expressed and is amenable to an exogenously administered probe. The next step requires an identification or development of new ligand(s) specific for that particular target and its radiolabeling with a suitable radiotracer to image the target.…”