{
  "abstract": "Background Assessing disease activity in giant cell arteritis (GCA) remains challenging, as existing clinical, laboratory and imaging biomarkers lack specificity. This proof-of-concept study explored the diagnostic potential of vascular adhesion protein-1 (VAP-1) targeting [ 68Ga]Ga-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) DOTA-sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) positron emission tomography-CT (PET/CT) as an inflammation-specific molecular imaging biomarker in newly diagnosed and relapsing GCA.Methods Patients with newly diagnosed GCA underwent [ 68Ga]Ga-DOTA-Siglec-9 PET/CT and vascular ultrasound. Tracer uptake (SUVmean/SUVmax) was quantified in aortic, supra-aortic and extravascular (shoulder/hip) regions and compared with relapsing patients. Levels of soluble VAP-1 (sVAP-1) and matrix metalloproteinase (MMP)2/MMP3/MMP9 were measured in patients and controls as potential biomarkers related to vascular inflammation.Results Eight patients with newly diagnosed GCA were compared with eight relapsing patients, alongside eight controls. Imaging revealed a positive association between ultrasound-assessed subclavian artery intima-media thickness and tracer uptake (r=0.67, p=0.035). Prednisolone exposure was inversely associated with vascular uptake across various vascular regions, with SUVmean showing a stronger overall negative association than SUVmax (SUVmean r=–0.51, p=0.043; SUVmax r=–0.62, p=0.010). Levels of sVAP-1 were reduced in newly diagnosed GCA compared with relapsing patients (p=0.0145) and controls (p=0.0446), and inversely associated with MMP2 (r=–0.56, p=0.037) and MMP9 (r=–0.47, p=0.089). Notably, MMP2 and MMP3 were negatively associated with vascular uptake (eg, aortic arch: r=–0.59, p=0.027).Conclusions This first-in-human study demonstrates that [ 68Ga]Ga-DOTA-Siglec-9 PET/CT detects vascular inflammation in GCA and shows attenuation with prednisolone exposure. Reduced sVAP-1 levels and inverse associations between MMP2/MMP3 and tracer uptake support a functional VAP-1/MMP axis underlying the imaging signal. Our findings further position [68Ga]Ga-DOTA-Siglec-9 PET/CT as a promising potential molecular imaging biomarker in GCA.",
  "authors": [
    {
      "affiliations": [
        "Medical Clinic and Polyclinic III Internal Medicine with a focus on Oncology, Hematology, and Rheumatology, Germany, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Simon M Petzinna"
    },
    {
      "affiliations": [
        "Clinic and Polyclinic for Nuclear Medicine, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Jim Küppers"
    },
    {
      "affiliations": [
        "Clinic and Polyclinic for Nuclear Medicine, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Benedikt Schemmer"
    },
    {
      "affiliations": [
        "University of Bonn, University Hospital Bonn, Medical Clinic and Polyclinic II Internal Medicine with a focus on Cardiology, Angiology and Pneumology, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Raul N Jamin"
    },
    {
      "affiliations": [
        "Medical Clinic and Polyclinic III Internal Medicine with a focus on Oncology, Hematology, and Rheumatology, Germany, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Sophie-Marie Kirch"
    },
    {
      "affiliations": [
        "Medical Clinic and Polyclinic III Internal Medicine with a focus on Oncology, Hematology, and Rheumatology, Germany, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Claus-Jürgen Bauer"
    },
    {
      "affiliations": [
        "Medical Clinic and Polyclinic III Internal Medicine with a focus on Oncology, Hematology, and Rheumatology, Germany, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Reza Gheitasi"
    },
    {
      "affiliations": [
        "Department of Rheumatology & Hiller-Research Unit Rheumatology, University Hospital of Düsseldorf, Düsseldorf, Germany"
      ],
      "name": "Anna L Kernder"
    },
    {
      "affiliations": [
        "Clinic and Polyclinic for Nuclear Medicine, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Daniel Ginzburg"
    },
    {
      "affiliations": [
        "Medical Clinic and Polyclinic III Internal Medicine with a focus on Oncology, Hematology, and Rheumatology, Germany, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Niklas T Baerlecken"
    },
    {
      "affiliations": [
        "Medical Clinic and Polyclinic III Internal Medicine with a focus on Oncology, Hematology, and Rheumatology, Germany, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Gustav B Jung"
    },
    {
      "affiliations": [
        "Medical Clinic and Polyclinic III Internal Medicine with a focus on Oncology, Hematology, and Rheumatology, Germany, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Maike S Adamson"
    },
    {
      "affiliations": [
        "Clinic and Polyclinic for Nuclear Medicine, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Markus Essler"
    },
    {
      "affiliations": [
        "Medical Clinic and Polyclinic III Internal Medicine with a focus on Oncology, Hematology, and Rheumatology, Germany, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Valentin S Schäfer"
    }
  ],
  "title": "[68Ga]Ga-DOTA-Siglec-9 PET/CT in newly diagnosed giant cell arteritis: an inflammation-specific, treatment-responsive molecular imaging biomarker",
  "uid": "cfee7094-1dac-51bf-9f2b-e662f07bac1f"
}