PT - JOURNAL ARTICLE AU - Riikka Viitanen AU - Olli Antero Moisio AU - Petteri Lankinen AU - Xiang-Guo Li AU - Mikko Koivumäki AU - Sami Suilamo AU - Tuula Tolvanen AU - Kirsi Taimen AU - Markku Mali AU - Ia Kohonen AU - Ilpo Koskivirta AU - Vesa Oikonen AU - Helena Virtanen AU - Kristiina Santalahti AU - Anu Autio AU - Antti Saraste AU - Laura Pirilä AU - Pirjo Nuutila AU - Juhani Knuuti AU - Sirpa Jalkanen AU - Anne Roivainen TI - First-in-Human Study of <sup>68</sup>Ga-DOTA-Siglec-9, PET Ligand Targeting Vascular Adhesion Protein 1 AID - 10.2967/jnumed.120.250696 DP - 2020 Aug 01 TA - Journal of Nuclear Medicine PG - jnumed.120.250696 4099 - http://jnm.snmjournals.org/content/early/2020/08/27/jnumed.120.250696.short 4100 - http://jnm.snmjournals.org/content/early/2020/08/27/jnumed.120.250696.full AB - 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, 68Ga-DOTA-Siglec-9, holds promise as a novel PET tracer for imaging of inflammation. This first-in-human 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 68Ga-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 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 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 able to detect arthritis comparable to 18F-FDG. Conclusion: Intravenous injection of 68Ga-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 68Ga-DOTA-Siglec-9 was within the same range as those 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, e.g., in trials aiming to elucidate the treatment efficacy of novel drug candidates.