Proof-of-concept PET imaging of pulmonary sarcoidosis using VAP-1-targeted radiotracer [68Ga]Ga-DOTA-Siglec-9

Prince Dadson; Heli Ylä-Outinen; Kari Kalliokoski; Terhi Tuokkola; Simona Malaspina; Mikko Koivumäki; Riikka Viitanen; Noora Rajala; Maria Silvoniemi; Tuula Tolvanen; Pirjo Nuutila; Sirpa Jalkanen; Antti Saraste; Tarja Saaresranta; Pekka Taimen; Anne Roivainen

doi:10.1186/s12931-025-03455-8

Proof-of-concept PET imaging of pulmonary sarcoidosis using VAP-1-targeted radiotracer [⁶⁸Ga]Ga-DOTA-Siglec-9

Respir Res. 2025 Dec 19. doi: 10.1186/s12931-025-03455-8. Online ahead of print.

Authors

Prince Dadson^{1

2

3}, Heli Ylä-Outinen⁴, Kari Kalliokoski¹, Terhi Tuokkola^{1

2}, Simona Malaspina^{1

2}, Mikko Koivumäki^{1

2}, Riikka Viitanen¹, Noora Rajala¹, Maria Silvoniemi⁴, Tuula Tolvanen^{2

5}, Pirjo Nuutila^{1

2

6}, Sirpa Jalkanen^{6

7}, Antti Saraste^{1

2

6

8}, Tarja Saaresranta^{4

9}, Pekka Taimen^{6

10}, Anne Roivainen^{11

12

13}

Affiliations

¹ Turku PET Centre, University of Turku, Turku, Finland.
² Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland.
³ Turku PET Centre, Åbo Akademi University, Turku, Finland.
⁴ Department of Pulmonary Diseases, Turku University Hospital, Turku, Finland.
⁵ Department of Medical Physics, Division of Medical Imaging, Turku University Hospital, Turku, Finland.
⁶ InFLAMES Research Flagship Center, University of Turku, Turku, Finland.
⁷ MediCity Research Laboratory, University of Turku, Turku, Finland.
⁸ Heart Center, Turku University Hospital and University of Turku, Turku, Finland.
⁹ Department of Pulmonary Diseases and Clinical Allergology, University of Turku, Turku, Finland.
¹⁰ Institute of Biomedicine, Department of Pathology, University of Turku, Turku University Hospital, Turku, Finland.
¹¹ Turku PET Centre, University of Turku, Turku, Finland. anne.roivainen@utu.fi.
¹² Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, Turku, FI-20521, Finland. anne.roivainen@utu.fi.
¹³ InFLAMES Research Flagship Center, University of Turku, Turku, Finland. anne.roivainen@utu.fi.

PMID: 41420234
DOI: 10.1186/s12931-025-03455-8

Abstract

Background: Sarcoidosis is a multisystem granulomatous disease of unknown etiology, with pulmonary involvement being the most common and clinically significant manifestation. Vascular adhesion protein-1 (VAP-1) plays a key role in leukocyte trafficking to inflamed tissues. [⁶⁸Ga]Ga-DOTA-Siglec-9 is a novel PET radiotracer that binds to VAP-1. This proof-of-concept study aimed to evaluate the feasibility of [⁶⁸Ga]Ga-DOTA-Siglec-9 PET/CT for imaging pulmonary sarcoidosis.

Methods: Six patients with stage 2 pulmonary sarcoidosis (age 50.5 ± 13.1 years; bodyweight 84.2 ± 14.7 kg), diagnosed by clinical, radiological, and histological findings, underwent [⁶⁸Ga]Ga-DOTA-Siglec-9 PET/CT. Control subjects included six healthy male volunteers (age 37.5 ± 10.3 years; bodyweight 80.3 ± 3.9 kg) and one female patient with lung cancer (age 77 years; bodyweight 62 kg). Tracer uptake was quantified in the lungs, mediastinal lymph nodes, and organs involved in systemic inflammation.

Results: Patients with sarcoidosis showed significantly higher [⁶⁸Ga]Ga-DOTA-Siglec-9 uptake in the lungs (SUV_mean 1.82 ± 0.52 vs. 0.41 ± 0.08; P = 0.00006) and mediastinal lymph nodes (SUV_mean 2.06 ± 0.46 vs. 0.89 ± 0.26; P = 0.0003) compared to healthy controls. Increased uptake was also observed in the liver (SUV_mean 1.18 ± 0.14 vs. 0.80 ± 0.10, P = 0.0003), spleen (SUV_mean 1.13 ± 0.09 vs. 0.82 ± 0.06, P = 0.00003), bone marrow (SUV_mean 0.30 ± 0.12 vs. 0.06 ± 0.05, P = 0.001), and bone (SUV_mean 0.27 ± 0.11 vs. 0.08 ± 0.04, P = 0.004), indicating systemic inflammation.

Conclusions: This proof-of-concept study demonstrates the potential of VAP-1-targeted [⁶⁸Ga]Ga-DOTA-Siglec-9 PET/CT for imaging pulmonary sarcoidosis and associated inflammatory activity. Further validation in larger cohorts are warranted.

Trial registration: ClinicalTrials.gov, NCT03755245 (registered 27 November 2018), NCT05212103 (registered 27 January 2022).

Keywords: Mediastinal lymph nodes; Positron emission tomography; Pulmonary sarcoidosis; Vascular adhesion protein 1; [68Ga]Ga-DOTA-Siglec-9.

Associated data

ClinicalTrials.gov/NCT03755245
ClinicalTrials.gov/NCT05212103

Abstract

Associated data

Grants and funding