PT  - JOURNAL ARTICLE
AU  - Lobeek, Daphne
AU  - Bouwman, Frédérique C.M.
AU  - Aarntzen, Erik H.J.G.
AU  - Molkenboer-Kuenen, Janneke D.M.
AU  - Flucke, Uta E.
AU  - Nguyen, Ha-Long
AU  - Vikkula, Miikka
AU  - Boon, Laurence M.
AU  - Klein, Willemijn
AU  - Laverman, Peter
AU  - Oyen, Wim J.G.
AU  - Boerman, Otto C.
AU  - Terry, Samantha Y.A.
AU  - SchultzeKool, Leo J.
AU  - Rijpkema, Mark
TI  - A Clinical Feasibility Study To Image Angiogenesis in Patients With Arteriovenous Malformations Using <sup>68</sup>Ga-RGD PET/CT.
AID  - 10.2967/jnumed.119.231167
DP  - 2019 Sep 01
TA  - Journal of Nuclear Medicine
PG  - jnumed.119.231167
4099  - http://jnm.snmjournals.org/content/early/2019/09/12/jnumed.119.231167.short
4100  - http://jnm.snmjournals.org/content/early/2019/09/12/jnumed.119.231167.full
AB  - 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 (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±1.1; mean SUVpeak 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 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.