@article {Lobeekjnumed.119.231167, author = {Daphne Lobeek and Fr{\'e}d{\'e}rique C.M. Bouwman and Erik H.J.G. Aarntzen and Janneke D.M. Molkenboer-Kuenen and Uta E. Flucke and Ha-Long Nguyen and Miikka Vikkula and Laurence M. Boon and Willemijn Klein and Peter Laverman and Wim J.G. Oyen and Otto C. Boerman and Samantha Y.A. Terry and Leo J. SchultzeKool and Mark Rijpkema}, title = {A Clinical Feasibility Study To Image Angiogenesis in Patients With Arteriovenous Malformations Using 68Ga-RGD PET/CT.}, elocation-id = {jnumed.119.231167}, year = {2019}, doi = {10.2967/jnumed.119.231167}, publisher = {Society of Nuclear Medicine}, abstract = {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{\textpm}5 MBq). Radiotracer uptake in AVM, blood-pool, and muscle activity were quantified as Standardized Uptake Values (SUVmax, SUVpeak) 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 αvβ3 integrin. Results: 68Ga-RGD PET/CT imaging showed enhanced radiotracer uptake in all AVM lesions (mean SUVmax 3.0{\textpm}1.1; mean SUVpeak 2.2{\textpm}0.9). Lesion/blood and lesion/muscle ratios were 3.5{\textpm}2.2 and 4.6{\textpm}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 αvβ3 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.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/early/2019/09/12/jnumed.119.231167}, eprint = {https://jnm.snmjournals.org/content/early/2019/09/12/jnumed.119.231167.full.pdf}, journal = {Journal of Nuclear Medicine} }