PET/SPECT imaging of hindlimb ischemia: focusing on angiogenesis and blood flow

Abstract

Peripheral artery disease (PAD) is a result of the atherosclerotic narrowing of blood vessels to the extremities, and the subsequent tissue ischemia can lead to the up-regulation of angiogenic growth factors and formation of new vessels as a recovery mechanism. Such formation of new vessels can be evaluated with various non-invasive molecular imaging techniques, where serial images from the same subjects can be obtained to allow the documentation of disease progression and therapeutic response. The most commonly used animal model for preclinical studies of PAD is the murine hindlimb ischemia model, and a number of radiotracers have been investigated for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of PAD. In this review article, we summarize the PET/SPECT tracers that have been tested in the murine hindlimb ischemia model as well as those used clinically to assess the extremity blood flow.

Treatment effect with anti-RAGE F(ab′)2 antibody improves hind limb angiogenesis and blood flow in Type 1 diabetic mice with left femoral artery ligation

“…Radionuclide probes to image angiogenesis in hind limb ischemia include SPECT and PET-labeled RGDs or peptomimetic proteins. 9,[14][15][16][17] Experimental studies using these probes have shown that quantitative estimates of tracer uptake on scans in the affected limbs correlate well with capillary sprouting. We therefore chose to estimate angiogenesis at 5 days after FAL (peak time for capillary sprouting) with imaging.…”

State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization

“…Molecular targeted imaging of angiogenesis has focused on EC targets (eg, VEGF, growth factor receptors, integrins, CD13, cell adhesion molecules), extracellular matrix proteins, and matrix proteases, or even associated non-EC targets (eg, monocytes, macrophages, and stem cells), and has been reviewed recently. [182][183][184] Several imaging modalities have been applied to evaluate angiogenesis and arteriogenesis in preclinical experimental animal models and are summarized in Table 7. Optical imaging approaches, in particular laser Doppler, have traditionally been used to evaluate changes in superficial perfusion associated with angiogenesis in models of hind-limb ischemia.…”

Positron Emission Tomography Imaging of Angiogenesis in a Murine Hindlimb Ischemia Model with 64Cu-Labeled TRC105

“…2, 3 However, assessing the efficacy of pro-angiogenic treatment has been challenging due to the lack of reliable, non-invasive imaging methods. 4, 5 …”

“…5–7 Non-invasive molecular imaging methods can provide information on the response of the ischemic tissues to the treatment, as well as detect molecular abnormalities that contribute to the early pathogenesis, thereby permitting early intervention. Positron emission tomography (PET) is a non-invasive, sensitive, and quantitative radionuclide-based imaging modality, 8, 9 which can be used to detect molecular changes during ischemia.…”