AB1295 ASSESSING GIANT CELL ARTERITIS ACTIVITY WITH [68GA]GA-DOTA-SIGLEC-9 PET-CT: A NOVEL IMAGING METHOD
Authors: S. M. Petzinna, J. Küppers, B. Schemmer, A. L. Kernder, C. J. Bauer, F. Gärtner, M. Essler, V. S. Schaefer
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Giant cell arteritis (GCA) is an immune-mediated granulomatous vasculitis affecting large and medium-sized vessels. Vascular ultrasound, the diagnostic gold standard, has limitations in evaluating the aorta. Therefore, positron emission tomography-computer tomography (PET-CT) with [<sup>18</sup>F]FDG has emerged as a diagnostic alternative. However, interpretation can be challenging as glucose metabolism also occurs in vascular remodeling. The novel radiotracer [<sup>68</sup>Ga]Ga-DOTA-Siglec-9 could improve PET-CT diagnostic capabilities. Early studies in animals and humans have validated its safety, tolerability, and potential efficacy in identifying inflammation. Siglec-9 is the leukocyte ligand for vascular adhesion protein 1 (VAP-1). Under physiological conditions, VAP-1 resides in intracellular vesicles within various cell types, including endothelial cells. Inflammatory stimuli prompt its translocation to the endothelial cell surface, enabling immune cell adhesion and migration. This upregulation of VAP-1 during inflammation renders [<sup>68</sup>Ga]Ga-DOTA-Siglec-9 PET-CT particularly interesting for GCA. <h3>Objectives:</h3> Evaluating [<sup>68</sup>Ga]Ga-DOTA-Siglec-9 PET-CT for Disease Activity Detection in Giant Cell Arteritis. <h3>Methods:</h3> We recruited a patient with recurrent GCA disease activity. The patient underwent a [<sup>68</sup>Ga]Ga-DOTA-Siglec-9 PET-CT scan with an injection of 120 MBq [<sup>68</sup>Ga]Ga-DOTA-Siglec-9. Fifty-one minutes post-injection, we conducted a low-dose CT for attenuation correction and a whole-body PET scan (one minute/ bed). We also used standard imaging methods, such as vascular ultrasound for the temporal, facial, axillary, carotid, and vertebral arteries, along with aortal MRI and routine laboratory tests. <h3>Results:</h3> A 90-year-old male patient with GCA, diagnosed in 2018, was enrolled. The patient reported recurrent GCA symptoms, including bitemporal headaches and night sweat. At the time of scan, he received methotrexate 15 mg per week and a daily dose of 2 mg prednisolone. His C-reactive protein level was elevated at 21 mg/l. [<sup>68</sup>Ga]Ga-DOTA-Siglec-9 PET scan revealed increased tracer uptake (SUVmax) in the subclavian artery (2.5), aortic arch (2.9), and heart (2.9), in contrast to an uptake of 1.5 in the liver (Figure 1). Notably, the increased uptake in the descending aorta (3.5) abruptly diminished to 2.2 when passing the diaphragm, with no changes in vessel caliber observed in CT (Figure 1). Vascular ultrasound and MRI did not reveal any pathological findings (data not shown). The injection of [<sup>68</sup>Ga]Ga-DOTA-Siglec-9 was well tolerated. Whole-body PET images of GCA patient (male, 90 years old) after intravenous injection of 120 MBq of [<sup>68</sup>Ga]Ga-DOTA-Siglec-9. Distribution of [<sup>68</sup>Ga]Ga-DOTA-Siglec-9 51 min after injection, based on imaging for one minute per bed position, revealed increased uptake in projection on the aortic and subclavian vessels and the heart. The increased uptake in the descending aorta diminishes abruptly while passing the diaphragm, without any caliber jump in the CT images. <h3>Conclusion:</h3> This study presents the first application of [<sup>68</sup>Ga]Ga-DOTA-Siglec-9 PET-CT in a GCA patient. PET-CT imaging demonstrated increased tracer uptake in the subclavian artery and aortic arch, with a localized and abrupt reduction. Notably, there were no corresponding findings in conventional imaging. We hypothesize that [<sup>68</sup>Ga]Ga-DOTA-Siglec-9 PET-CT might offer unique potential for precise, localized mapping of affected vascular tissue in GCA, especially during relapse. This could revolutionize the current diagnostic approach, leading to more targeted strategies for monitoring disease activity. Given these encouraging findings, larger scale studies are essential to fully elucidate the potential role of [<sup>68</sup>Ga]Ga-DOTA-Siglec-9 PET-CT in the diagnostic landscape of GCA. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>