First-in-Humans Study of ⁶⁸Ga-DOTA-Siglec-9, a PET Ligand Targeting Vascular Adhesion Protein 1

Abstract

Sialic acid-binding immunoglubulin-like lectin 9 (Siglec-9) is a ligand of vascular adhesion protein 1 (VAP-1). A gallium 68-labeled peptide of Siglec-9, 68 Ga-DOTA-Siglec-9, holds promise as a novel PET tracer for imaging of inflammation. This first-inhuman study investigated the safety, tolerability, biodistribution, and radiation dosimetry of this radiopharmaceutical. Methods: Six healthy males underwent dynamic whole-body PET/CT. Serial venous blood samples were drawn from 1-240 min after intravenous injection of 162 ± 4 MBq of 68 Ga-DOTA-Siglec-9. In addition to gamma counting, the plasma samples were analyzed by high-performance liquid chromatography to detect intact tracer and radioactive metabolites. Radiation doses were calculated using the OLINDA/EXM 2.2 software. In addition, a patient with early rheumatoid arthritis was studied with both 68 Ga-DOTA-Siglec-9 and 18 F-FDG PET/CT to determine the ability of the new tracer to detect arthritis. Results: 68 Ga-DOTA-Siglec-9 was well tolerated by all subjects. 68 Ga-DOTA-Siglec-9 was rapidly cleared from blood circulation and several radioactive metabolites were detected. The organs with the highest absorbed doses were the urinary bladder wall (0.38 mSv/MBq) and kidneys (0.054 mSv/MBq). The mean effective dose was 0.022 mSv/MBq (range 0.020-0.024 mSv/MBq). Most importantly, however, 68 Ga-DOTA-Siglec-9 was able to detect arthritis comparable to 18 F-FDG. Conclusion: Intravenous injection of 68 Ga-DOTA-Siglec-9 was safe and biodistribution is favorable for testing of the tracer in larger group of patients with rheumatoid arthritis planned in the next phase of clinical trials. The effective radiation dose of 68 Ga-DOTA-Siglec-9 was within the same range as those of other 68 Ga-labeled tracers. Injection of 150 MBq of 68 Ga-DOTA-Siglec-9 would expose a subject to 3.3 mSv. These findings support the possible repeated clinical use of 68 Ga-DOTA-Siglec-9, e.g., in trials aiming to elucidate the treatment efficacy of novel drug candidates.

[68Ga]Ga-4HMSA a promising new PET tracer for imaging inflammation

“…Consequently, the development of more sensitive radiotracers for molecular imaging of inflammation by positron emission tomography (PET) may provide new insights into the detection and the treatment at early stage disease [ 1 ]. Over the past years, many radiopharmaceuticals including 2-deoxy-2-[ 18 F]fluoro- d -glucose ([ 18 F]FDG) and 68 Ga-based tracers [ 2 ] have received considerable attention and some of them have shown promising results in the field of inflammation imaging [ 3 – 7 ].…”

Systematic Review: Targeted Molecular Imaging of Angiogenesis and Its Mediators in Rheumatoid Arthritis

“…The in vivo stability test of the tracers in plasma by HPLC analysis revealed, within 10 min, several peaks representing metabolites other than the radiotracer. The tracer pharmacokinetics performed in healthy men exhibited rapid renal clearance due to the hydrophilic and small size of the peptide [73]. A 30 min dynamic PET/CT scan of the hands of the RA patient showed uptake in the arthritic phalangeal joints.…”

“…Recently, the first-in-human study of 68 Ga-DOTA-Siglec-9 was performed in order to detect early stage arthritis [73]. 68 Ga-DOTA-Siglec-9 PET/CT and 18 F-FDG PET/CT were performed in one patient with RA.…”

Radiotracers for Bone Marrow Infection Imaging

“…[ 68 Ga]Ga-DOTA-Siglec-9 has recently been tested in humans, finding the application safe and demonstrating that the tracer could image rheumatoid arthritis with the uptake visually comparable to uptake of [ 18 F]FDG [ 76 ].…”