RT Journal Article SR Electronic T1 First-in-Humans Study of 68Ga-DOTA-Siglec-9, a PET Ligand Targeting Vascular Adhesion Protein 1 JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 577 OP 583 DO 10.2967/jnumed.120.250696 VO 62 IS 4 A1 Viitanen, Riikka A1 Moisio, Olli A1 Lankinen, Petteri A1 Li, Xiang-Guo A1 Koivumäki, Mikko A1 Suilamo, Sami A1 Tolvanen, Tuula A1 Taimen, Kirsi A1 Mali, Markku A1 Kohonen, Ia A1 Koskivirta, Ilpo A1 Oikonen, Vesa A1 Virtanen, Helena A1 Santalahti, Kristiina A1 Autio, Anu A1 Saraste, Antti A1 Pirilä, Laura A1 Nuutila, Pirjo A1 Knuuti, Juhani A1 Jalkanen, Sirpa A1 Roivainen, Anne YR 2021 UL http://jnm.snmjournals.org/content/62/4/577.abstract AB Sialic acid–binding immunoglubulinlike lectin 9 (Siglec-9) is a ligand of vascular adhesion protein 1. A 68Ga-labeled peptide of Siglec-9, 68Ga-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 68Ga-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 68Ga-DOTA-Siglec-9 and 18F-FDG PET/CT to determine the ability of the new tracer to detect arthritis. Results: 68Ga-DOTA-Siglec-9 was well tolerated by all subjects. 68Ga-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, 68Ga-DOTA-Siglec-9 was comparable to 18F-FDG in detecting arthritis. Conclusion: Intravenous injection of 68Ga-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 68Ga-DOTA-Siglec-9 was within the same range as the effective radiation doses of other 68Ga-labeled tracers. Injection of 150 MBq of 68Ga-DOTA-Siglec-9 would expose a subject to 3.3 mSv. These findings support the possible repeated clinical use of 68Ga-DOTA-Siglec-9, such as in trials to elucidate the treatment efficacy of novel drug candidates.