Pilot feasibility study investigating 68 Ga-NODAGA-RGD PET-computed tomography molecular angiogenesis imaging in patients with peripheral arterial diseases: can it be of potential clinical value?

INTRODUCTION: Peripheral arterial disease (PAD) is a common vascular condition caused mainly by atherosclerosis that can cause ischemia and increase cardiovascular risk. Noninvasive imaging, such as Doppler ultrasonography, provides hemodynamic information but lack molecular insight. Integrin αvβ3 expression reflects angiogenesis in ischemic tissue and radiolabeled RGD peptides can be used to visualize this process noninvasively. This study prospectively assessed the diagnostic performance of 68 Ga-NODAGA-RGD PET-computed tomography (CT) in patients with suspected or proven PAD and correlate the findings to clinical and Doppler findings.

MATERIALS AND METHODS: Thirty patients aged 26-87 years (23 males and 7 females, median age 52 years) presented with clinical or Doppler findings that were consistent with PAD underwent an imaging study with 68 Ga-NODAGA-RGD PET-CT 60 ± 15 min following the injection of a radiotracer dose of 3-5 mCi. Tracer uptake was visually rated on a four-point scale relative to liver and spleen activity and the maximum standardized uptake (SUV max ) was documented. Using the clinical and Doppler findings as gold standard diagnostic indices were calculated. An agreement analysis was performed using Cohen's κ and McNemar's test.

RESULTS: Fifteen patients had PAD and 15 had non-PAD (tumor-induced thrombosis - 1, cellulitis - 9, diabetic foot - 3, arthritis - 2). 68 Ga-NODAGA-RGD PET-CT was positive in 11 of 15 PAD patients (true positives) and negative in 15 of the 15 non-PAD patients (true negatives), with zero false positives and four false negatives. The sensitivity, specificity, and positive predictive values were 73.34%, 100%, and 100%, respectively. False negatives were primarily associated with acute ischemia lacking angiogenesis.

CONCLUSION: 68 Ga-NODAGA-RGD PET-CT shows potential value and agreement with Doppler and clinical assessment for detecting PAD and may serve as a potential molecular imaging modality to evaluate angiogenesis and the disease extent as a complementary diagnostic imaging modality. Although RGD tracers have been explored for theranostic applications in oncology, the uptake levels observed in PAD in this study were generally low and currently do not support such applications. It also provides an evaluation of systemic vascularity outside of localized segments. Larger studies are warranted to validate its disease management implications.