Daphne Lobeek1, Frédérique C M Bouwman2, Erik H J G Aarntzen2, Janneke D M Molkenboer-Kuenen2, Uta E Flucke3, Ha-Long Nguyen4, Miikka Vikkula4,5, Laurence M Boon4,5, Willemijn Klein2,6, Peter Laverman2, Wim J G Oyen2,7,8, Otto C Boerman2, Samantha Y A Terry9, Leo J Schultze Kool2,6, Mark Rijpkema2. 1. Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands daphne.lobeek@radboudumc.nl. 2. Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. 3. Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands. 4. Human Molecular Genetics, de Duve Institute, University of Louvain, Brussels, Belgium. 5. Centre for Vascular Anomalies (part of VASCERN European Reference Network), Division of Plastic Surgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium. 6. Centre for Vascular Anomalies (part of VASCERN European Reference Network), Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. 7. Department of Biomedical Sciences, Humanitas University, Milan, Italy. 8. Department of Radiology and Nuclear Medicine, Rijnstate Hospital, Arnhem, The Netherlands; and. 9. Department of Imaging Chemistry and Biology, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom.
Abstract
Arteriovenous malformations (AVMs) have an inherent capacity to form new blood vessels, resulting in excessive lesion growth, and this process is further triggered by the release of angiogenic factors. 68Ga-labeled arginine-glycine-aspartate tripeptide sequence (RGD) PET/CT imaging may provide insight into the angiogenic status and treatment response of AVMs. This clinical feasibility study was performed to demonstrate 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 y; 4 men and 6 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). Uptake in the AVM, blood pool, and muscle was quantified as SUVmax and SUVpeak, and a descriptive analysis of the PET/CT images was performed. Furthermore, immunohistochemical analysis was performed on surgical biopsy sections of peripheral AVMs to investigate the expression pattern of integrin αvβ3 Results: 68Ga-RGD PET/CT imaging showed enhanced uptake in all AVM lesions (mean SUVmax, 3.0 ± 1.1; mean SUVpeak, 2.2 ± 0.9). Lesion-to-blood and lesion-to-muscle ratios were 3.5 ± 2.2 and 4.6 ± 2.8, respectively. Uptake in blood and muscle was significantly higher in AVMs than in background tissue (P = 0.0006 and P = 0.0014, respectively). Initial observations included uptake in multifocal AVM lesions and enhanced uptake in intraosseous components in those AVM cases affecting bone integrity. Immunohistochemical analysis revealed cytoplasmatic and membranous integrin αvβ3 expression in the endothelial cells of AVMs. Conclusion: This feasibility study showed increased uptake in AVMs with angiogenic activity, compared with surrounding tissue without angiogenic activity, suggesting that 68Ga-RGD PET/CT imaging can be used as a tool to quantitatively determine angiogenesis in AVMs. Further studies will be conducted to explore the potential of 68Ga-RGD PET/CT imaging for guiding current treatment decisions and for assessing response to antiangiogenic treatment.
Arteriovenous malformations (AVMs) have an inherent capacity to form new blood vessels, resulting in excessive lesion growth, and this process is further triggered by the release of angiogenic factors. 68Ga-labeled arginine-glycine-aspartate tripeptide sequence (RGD) PET/CT imaging may provide insight into the angiogenic status and treatment response of AVMs. This clinical feasibility study was performed to demonstrate 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 y; 4 men and 6 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). Uptake in the AVM, blood pool, and muscle was quantified as SUVmax and SUVpeak, and a descriptive analysis of the PET/CT images was performed. Furthermore, immunohistochemical analysis was performed on surgical biopsy sections of peripheral AVMs to investigate the expression pattern of integrin αvβ3 Results: 68Ga-RGD PET/CT imaging showed enhanced uptake in all AVM lesions (mean SUVmax, 3.0 ± 1.1; mean SUVpeak, 2.2 ± 0.9). Lesion-to-blood and lesion-to-muscle ratios were 3.5 ± 2.2 and 4.6 ± 2.8, respectively. Uptake in blood and muscle was significantly higher in AVMs than in background tissue (P = 0.0006 and P = 0.0014, respectively). Initial observations included uptake in multifocal AVM lesions and enhanced uptake in intraosseous components in those AVM cases affecting bone integrity. Immunohistochemical analysis revealed cytoplasmatic and membranous integrin αvβ3 expression in the endothelial cells of AVMs. Conclusion: This feasibility study showed increased uptake in AVMs with angiogenic activity, compared with surrounding tissue without angiogenic activity, suggesting that 68Ga-RGD PET/CT imaging can be used as a tool to quantitatively determine angiogenesis in AVMs. Further studies will be conducted to explore the potential of 68Ga-RGD PET/CT imaging for guiding current treatment decisions and for assessing response to antiangiogenic treatment.
Authors: Daphne Lobeek; Gerben M Franssen; Michelle T Ma; Hans-Jürgen Wester; Clemens Decristoforo; Wim J G Oyen; Otto C Boerman; Samantha Y A Terry; Mark Rijpkema Journal: J Nucl Med Date: 2018-04-06 Impact factor: 10.057
Authors: Nikolaos Mouchtouris; Pascal M Jabbour; Robert M Starke; David M Hasan; Mario Zanaty; Thana Theofanis; Dale Ding; Stavropoula I Tjoumakaris; Aaron S Dumont; George M Ghobrial; David Kung; Robert H Rosenwasser; Nohra Chalouhi Journal: J Cereb Blood Flow Metab Date: 2014-11-19 Impact factor: 6.200
Authors: Oscar Arrieta; Francisco O Garcia-Perez; David Michel-Tello; Laura-Alejandra Ramírez-Tirado; Quetzali Pitalua-Cortes; Graciela Cruz-Rico; Eleazar-Omar Macedo-Pérez; Andrés F Cardona; Jaime de la Garza-Salazar Journal: J Nucl Med Date: 2017-08-17 Impact factor: 10.057
Authors: Patricia E Burrows; John B Mulliken; Steven J Fishman; Giannoula L Klement; Judah Folkman Journal: J Craniofac Surg Date: 2009-03 Impact factor: 1.046
Authors: Ingrid Dijkgraaf; Cheng-Bin Yim; Gerben M Franssen; Robert C Schuit; Gert Luurtsema; Shuang Liu; Wim J G Oyen; Otto C Boerman Journal: Eur J Nucl Med Mol Imaging Date: 2010-09-21 Impact factor: 9.236
Authors: Vanessa F Schmidt; Max Masthoff; Michael Czihal; Beatrix Cucuruz; Beate Häberle; Richard Brill; Walter A Wohlgemuth; Moritz Wildgruber Journal: Mol Cell Pediatr Date: 2021-12-07