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Vascular PET/CT and SPECT/CT
Conventional radiological imaging modalities for the assessment of blood vessels have focused on size, irregularity of the vascular lumen, and anatomic changes in adjacent structures. The ability of these morphologic imaging techniques to identify physiologic changes such as active inflammatory processes and plaques at risk for rupture is, however, limited. Molecular imaging has the advantage of enabling noninvasive physiologic assessment of these processes with radionuclides, very often early in the course of disease. Such early assessment can lead to subsequent changes in clinical management, potentially affecting patients’ outcomes.
The limitations of traditional nuclear medicine techniques, mainly low spatial resolution and lack of anatomic details, have been overcome in the last decade with the introduction of the hybrid single-photon emission computed tomography/computed tomography (SPECT/CT) and positron emission tomography (PET)/CT imaging devices. A large body of evidence has accumulated on the use of molecular tracers for the assessment of vascular inflammation and infection (especially in vascular graft infections and vasculitis), early diagnosis, precise determination of the extent of disease, and assessment of response to therapy.
Basic Principles
Single-Photon Emission Computed Tomography, Positron Emission Tomography, and Hybrid Imaging
In nuclear medicine imaging, radiopharmaceuticals are administered to the patient intravenously. Images are obtained from radiation, which is emitted at the location of disease processes in the patient’s body. Two main camera systems, the gamma camera and the PET camera, convert this radiation into images.
The gamma camera forms the basis of conventional nuclear medicine and provides two-dimensional imaging of the body. Image contrast of this planar imaging is rather low due to the presence of overlying structures that interfere with the region of interest. This limitation can be overcome by collecting images from different angles around the patient, the so-called SPECT, which leads to better spatial resolution, higher contrast, and improved sensitivity.
PET is an imaging tool based on radionuclides that emit positrons to become stable. For example, decay of the radioisotope fluorine-18 ( 18 F) leads to emission of a positron that collides with an electron after traveling a short distance in tissue, thereby generating a pair of 511-keV annihilating photons (in opposite directions) that can be detected by the PET imaging device. The major advantage of PET over SPECT is that the PET camera system is more effective in detecting photons and provides better spatial resolution (around 3–4 mm). Furthermore, quantification is easier with PET. Uptake of PET radiopharmaceuticals can be quantified by standardized uptake values (SUVs), which measure the tracer uptake within a region of interest in relation to the injected dose and patient’s body weight.
However, both modalities provide only very limited morphologic information. Therefore PET as well as SPECT are now combined with CT in a single imaging modality. Hybrid SPECT/CT, PET/CT, and now also emerging PET/magnetic resonance imaging (MRI) improve the sensitivity by anatomic detection of small structures, such as plaques, and may also improve the specificity, confirming active disease in these small lesions. Other advantages of combining radiologic and nuclear medicine techniques in one imaging modality are reduced costs, perfect correlation of pathophysiologic with anatomic information, and the one-stop-shop principle, which is convenient for the patient and reduces waiting time.
Most Commonly Used Tracers for Vascular Diseases
18 F-Fluorodeoxyglucose
Fluorodeoxyglucose (FDG) is an analogue of glucose, taken up by and accumulating in cells in proportion to their metabolic activity. The transfer of glucose into cells is facilitated by glucose transporters (GLUTs) and sodium glucose cotransporters (SGLTs). After entering the cell, glucose undergoes phosphorylation by hexokinase, forming glucose-6-phosphate. After its glycolysis by hexose-6-phosphate isomerase, fructose-6 phosphate is formed. In contrast, the analogue 2-deoxy- d -glucose cannot undergo conversion by hexose-6-phosphate isomerase; therefore, FDG becomes trapped in the cytosol. Glucose and FDG have otherwise similar properties, and the rates of phosphorylation in vivo are proportional to each other, reflecting the general rates of glucose metabolism.
FDG imaging is today the “gold standard” in the assessment of patients with cancer, for staging tumors, monitoring response to treatment, and diagnosing recurrence. FDG also has an increasing role in infectious and inflammation diseases, since many cells involved in infection and inflammation (activated leukocytes, monocytes, lymphocytes, macrophages, and giant cells) use glucose for their metabolism. This tracer is extensively used in vascular inflammation and infection imaging.
18 F-Sodium Fluoride
Sodium fluoride (NaF) is mainly used for skeletal imaging, since it has the desirable characteristics of high and rapid bone uptake accompanied by a very rapid blood clearance, which results in a high bone-to-background ratio. Its use in vascular imaging is, at this time, limited to plaque imaging due to uptake in the calcifications. Since NaF is not physiologically taken up in the myocardium and blood vessels, it could also potentially be a better agent than FDG in assessing the coronary vessels.
Labeled White Blood Cells
Scintigraphy using autologous white blood cells – also called “leukocyte scintigraphy” – is still considered the gold standard nuclear imaging modality for infections. In using the correct acquisition protocols and interpretation criteria, this technique is highly accurate. Limitations, however, are the needs for a laborious labeling procedure and for imaging at several time points. White blood cell scintigraphy is primarily used in musculoskeletal infections but has also been evaluated in vascular diseases, such as vascular graft infections.
Other Available Tracers
Besides the already mentioned commonly used tracers, various other radiopharmaceuticals have been developed and tested, most of them in atherosclerosis. SPECT and PET imaging of atherosclerosis takes advantage of the wide array of biologic mechanisms involved in the different stages of atherosclerosis and plaque formation. Tracers have been developed for targeting the atherosclerotic lesion components, such as technetium-99m ( 99m Tc)-labeled low-density lipoprotein (LDL), 99m Tc-labeled oxidized LDL, labeled antibodies against plaques and degradation products, and labeled interleukin-2 to detect activated lymphocytes at the site of a vulnerable plaque. Since an unstable plaque with rupture or erosion of the fibrous cap demonstrates activation of platelets and of the clotting cascade, other studies have focused on labeled platelets and fibrins. Apoptosis has also been demonstrated in macrophages as well as in smooth muscle cells of atherosclerotic plaques and is often observed in the fibrous cap of a ruptured plaque. Therefore, 99m Tc-labeled annexin V has also been used for specifically targeting the atherosclerotic plaque. Also matrix metalloproteinases (MMPs), excreted by macrophages and activated by plasmin as part of the inflammatory process in active atherosclerotic lesions, were labeled and tested. Many of the molecular probes developed for plaque imaging are linked with inflammation, a major component of vulnerable plaques. Labeled macrophages, monocytes, and lymphocytes were all used for imaging the inflammatory process. An overview of all the possible radiopharmaceuticals for imaging atherosclerosis can be found in an extensive review.
Clinical Applications
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