A Clinical Feasibility Study to Image Angiogenesis in Patients with Arteriovenous Malformations Using 68Ga-RGD PET/CT

Daphne Lobeek; Frédérique C M Bouwman; Erik H J G Aarntzen; Janneke D M Molkenboer-Kuenen; Uta E Flucke; Ha-Long Nguyen; Miikka Vikkula; Laurence M Boon; Willemijn Klein; Peter Laverman; Wim J G Oyen; Otto C Boerman; Samantha Y A Terry; Leo J Schultze Kool; Mark Rijpkema

doi:10.2967/jnumed.119.231167

A Clinical Feasibility Study to Image Angiogenesis in Patients with Arteriovenous Malformations Using ⁶⁸Ga-RGD PET/CT

J Nucl Med. 2020 Feb;61(2):270-275. doi: 10.2967/jnumed.119.231167. Epub 2019 Sep 13.

Authors

Daphne Lobeek¹, Frédérique C M Bouwman², Erik H J G Aarntzen², Janneke D M Molkenboer-Kuenen², Uta E Flucke³, Ha-Long Nguyen⁴, Miikka Vikkula^{4

5}, Laurence M Boon^{4

5}, Willemijn Klein^{2

6}, Peter Laverman², Wim J G Oyen^{2

7

8}, Otto C Boerman², Samantha Y A Terry⁹, Leo J Schultze Kool^{2

6}, Mark Rijpkema²

Affiliations

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 SUV_max and SUV_peak, 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 α_vβ₃Results:⁶⁸Ga-RGD PET/CT imaging showed enhanced uptake in all AVM lesions (mean SUV_max, 3.0 ± 1.1; mean SUV_peak, 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 α_vβ₃ 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.

Keywords: PET/CT; RGD; angiogenesis; arteriovenous malformation; integrin αvβ3.

Publication types

Clinical Trial

MeSH terms

Adult
Arteriovenous Malformations / complications
Arteriovenous Malformations / diagnostic imaging*
Arteriovenous Malformations / metabolism
Feasibility Studies
Female
Humans
Male
Middle Aged
Neovascularization, Pathologic / complications
Neovascularization, Pathologic / diagnostic imaging*
Oligopeptides* / metabolism
Positron Emission Tomography Computed Tomography*
Prospective Studies
Protein Transport
Young Adult

Substances

Oligopeptides
arginyl-glycyl-aspartic acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding