A Clinical Feasibility Study To Image Angiogenesis in Patients With Arteriovenous Malformations Using 68Ga-RGD PET/CT.

Objective: Arteriovenous Malformations (AVMs) have an inherent capacity to form new blood vessels resulting in excessive lesion growth and this is further triggered by the release of angiogenic factors. Gallium-68 (⁶⁸Ga) labeled arginine-glycine-aspartate tripeptide sequence (RGD) positron emission tomography (PET)/computed tomography (CT) imaging (⁶⁸Ga-RGD PET/CT) may provide insight in the angiogenic and hemodynamic status and treatment response of AVMs. This clinical feasibility study demonstrates that ⁶⁸Ga-RGD PET/CT imaging can be used to quantitatively assess angiogenesis in peripheral AVMs. Methods: Ten patients with a peripheral AVM (mean age 40 years, four men, six women) and scheduled for endovascular embolization treatment, were prospectively included. All patients underwent ⁶⁸Ga-RGD PET/CT imaging 60 min after injection (mean dose 207±5 MBq). Radiotracer uptake in AVM, blood-pool, and muscle activity were quantified as Standardized Uptake Values (SUV_max, SUV_peak) and descriptive analysis of the PET/CT images was performed. Furthermore, immunohistochemical analysis was performed on surgical biopsy material of peripheral AVMs to investigate the expression pattern of integrin α_vβ₃ integrin. Results:⁶⁸Ga-RGD PET/CT imaging showed enhanced radiotracer uptake in all AVM lesions (mean SUV_max 3.0±1.1; mean SUV_peak 2.2±0.9). Lesion/blood and lesion/muscle ratios were 3.5±2.2 and 4.6±2.8, respectively. Radiotracer uptake in AVMs was significantly higher compared to uptake in background tissue (p=0.0006 and p=0.0014) for blood and muscle, respectively. Initial observations include identification of radiotracer uptake in (multifocal) AVM lesions and enhanced radiotracer uptake in intra-osseous components in those AVM cases affecting the bone integrity. Immunohistochemical analysis revealed cytoplasmatic and cell membranous integrin α_vβ₃ integrin expression in endothelial cells of AVMs. Conclusion: This feasibility study showed increased radiotracer uptake in AVM with angiogenic activity compared to surrounding tissue without angiogenic activity, suggesting that ⁶⁸Ga-RGD PET/CT imaging can be used as a tool to quantitatively determine angiogenesis in AVM. Further studies will be conducted to explore the potential of ⁶⁸Ga-RGD PET/CT imaging for guiding current treatment decisions and for assessment of response to anti-angiogenic treatment.