Noninvasive Evaluation of Angiogenesis and Therapeutic Response after Hindlimb Ischemia with an Integrin-Targeted Tracer by PET

Background: Peripheral arterial disease (PAD) can severely compromise limb vitality and function. Angiogenesis plays an important role in healing of ischemic lesions. Radiolabeled RGD (Arg-Gly-Asp) peptides specifically targeting αvβ3 integrin are promising tracers for imaging angiogenesis. In this study, we investigated the application a one-step labeled evaluation angiogenesis therapy response mouse model hindlimb ischemia (HI) by positron emission tomography (PET). Methods: HI was induced ablation femoral artery mice. PET using 18F-AlF-NOTA-PRGD2 (18F-PRGD2) tracer performed at day 0 (pre-surgery) days 3, 7, 14, 21 after surgery to evaluate longitudinally noninvasively. The control peptide RAD (Arg-Ala-Asp) with similar procedure block agent were used confirm specific binding 18F-PRGD2 integrin. Ex vivo CD31 staining detect addition, angiogenic monitored immunofluorescence data. Results: successful establishment confirmed ultrasound laser doppler perfusion (LDPI). Specific validated minimal uptake significant decrease accumulation when added. Local 18F-RRGD2 detected as early 3 reached peak 7 surgery. temporal change focal positively correlated pattern vascular density. Moreover, endothelial growth factor (VEGF) treatment increased enhanced angiogenesis, which is consistent β3 expression. Conclusions: targeted αvβ3integrin allows longitudinal monitoring ischemia-induced noninvasive assessment VEGF ischemia. simple synthesis performance enables feasibility future clinical translation cardiovascular diseases.