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

TL;DR

A new PET imaging technique using a radiotracer targeting VAP-1 shows promise for detecting inflammation in pulmonary sarcoidosis.

Contribution

This study introduces [68Ga]Ga-DOTA-Siglec-9 as a novel PET radiotracer for imaging pulmonary sarcoidosis by targeting VAP-1.

Findings

Sarcoidosis patients showed significantly higher tracer uptake in lungs and mediastinal lymph nodes compared to healthy controls.

Increased uptake was also observed in liver, spleen, bone marrow, and bone, indicating systemic inflammation.

The radiotracer demonstrated potential for imaging inflammatory activity in pulmonary sarcoidosis.

Abstract

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.

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.

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

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 is warranted.

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

The online version contains supplementary material available at 10.1186/s12931-025-03455-8.

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