Probing for peripheral vascular disease with PET and SPECT

There is growing interest in applying molecular imaging techniques for the detection of peripheral vascular disease (PVD). A range of scanner-tracer combinations can be used for perfusion, angiogenesis and atherosclerotic imaging, according to a review published online Oct. 7 in the Journal of Nuclear Medicine.

A team of researchers, including Mitchel R. Stacy, PhD, from the department of internal medicine at Yale School of Medicine in New Haven, Conn., set out to review radiotracers as a means of detecting the often underdiagnosed and progressive atherosclerotic disease.

“Radiotracer imaging of the lower extremities with techniques such as PET and SPECT can provide a noninvasive quantitative technique for the evaluation of the pathophysiology associated with PVD and may complement clinical indices and other imaging approaches,” wrote Stacy et al.

Several modalities are used to screen and track PVD, including ankle–brachial indices and duplex ultrasound, PET, SPECT, MR and CT. All of these options have their own respective limitations. CT and MR provide high special resolution, but quantitative CT data is not often available and MR is limited by a lack of sensitivity when used for resting perfusion studies. Ankle-brachial indices are relatively insensitive for gauging medial calcification and microvessel disease and ultrasound is a popular choice because it is a comparatively inexpensive modality that is fast and accessible, but it lacks depth of imaging and can only be used for blood-vessels with significant flow. PET and SPECT are significantly more sensitive, and now with the union of CT and MR in newer hybrid systems, clinicians can fill in the structural blanks and provide attenuation correction.

“Nuclear imaging approaches provide high sensitivity and, when applied with biologically targeted radiotracers, offer potentially novel methods for the investigation of PVD, with integration of perfusion and assessment of tissue oxygenation, metabolism, or biologic processes such as angiogenesis,” wrote the authors

Between SPECT and PET, SPECT allows for the possibility of dual-tracer imaging and a lower cost structure and PET provides higher sensitivity at a lower dose. The authors noted a wide range of molecular imaging agents for both modalities in the areas of perfusion imaging, detection of angiogenesis and atherosclerosis imaging. A method of 3D SPECT with Tl-201 was noted for its usefulness in imaging lower-extremity ischemia. For multiple SPECT imaging studies, Tc-99m was recommended due to its relatively long half-life and high image quality. For evaluating variance in flow reserve in the lower legs, O-15 water was found to be beneficial.

In angiogenesis imaging, using vascular endothelial growth factor (VEGF) ligands was found to be especially effective. A number of techniques are available, but the authors noted the use In-l11 labeled recombinant human VEGF121, which is an angiogenic protein involved in hypoxia that attaches to VEGF receptors. This method is still in the preclinical phase. Integrin imaging was mentioned as a viable means of imaging angiogenesis and the use of nanoprobes in this area is also an emerging practice.

Other developing techniques include imaging for vulnerable plaques, which provides an additional preventative edge against rupture. In a similar vein, FDG PET/CT was revealed to have some potential for the detection of deep vein thrombosis. Further study is needed to elucidate the full potential of molecular imaging for PVD.

“Continuing development of radiotracer imaging of PVD may provide effective, noninvasive techniques for evaluating serial responses to various forms of medical therapy, such as revascularization, exercise programs, and novel gene- or cell-based drug therapies. The high sensitivity of SPECT and PET imaging may be ideally suited for evaluation of these therapies and could complement anatomic and clinical indices for improved assessment of physiologic changesin PVD patients, providing potential guidance for vascular interventions as well as targeted delivery of drug therapies in the future,” the authors concluded.