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

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

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.

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