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

Sialic acid–binding immunoglubulinlike lectin 9 (Siglec-9) is a ligand of vascular adhesion protein 1. A (68)Ga-labeled peptide of Siglec-9, (68)Ga-DOTA-Siglec-9, holds promise as a novel PET tracer for imaging of inflammation. This first-in-humans study investigated the safety, tolerability, biodistribution, and radiation dosimetry of this radiopharmaceutical. Methods: Six healthy men underwent dynamic whole-body PET/CT. Serial venous blood samples were drawn from 1 to 240 min after intravenous injection of 162 ± 4 MBq of (68)Ga-DOTA-Siglec-9. In addition to γ-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 software, version 2.2. 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 the 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 comparable to (18)F-FDG in detecting arthritis. Conclusion: Intravenous injection of (68)Ga-DOTA-Siglec-9 was safe and biodistribution was favorable for testing of the tracer in larger group of patients with rheumatoid arthritis, as is planned for the next phase of clinical trials. The effective radiation dose of (68)Ga-DOTA-Siglec-9 was within the same range as the effective radiation doses 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, such as in trials to elucidate the treatment efficacy of novel drug candidates.