TY - JOUR T1 - First in human dosimetry of <sup>18</sup>F-NKO-035: a new PET probe targeting L-type amino acid transporter 1 (LAT1) <strong/> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 627 LP - 627 VL - 61 IS - supplement 1 AU - Tadashi Watabe AU - Sadahiro Naka AU - Fumihiko Soeda AU - Takashi Kamiya AU - Hidetaka Sasaki AU - Daisuke Katayama AU - Hiroki Kato AU - Mitsuaki Tatsumi AU - Eku Shimosegawa AU - Yoshikatsu Kanai AU - Jun Hatazawa Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/627.abstract N2 - 627Objectives: Although 18F-FDG is the most common PET probe in oncology, it sometimes shows false positive uptakes in the inflammatory lesions. To overcome this disadvantage, tumor-specific PET probes have been developed targeting L-type amino acid transporter-1 (LAT1). LAT1 expression was observed in many types of cancers, especially metastatic tumors, but not in normal tissues. Our group recently succeeded in the synthesis of 18F-NKO-035, a new PET probe targeting LAT1, with high radiochemical yield and high molar activity from 18F-. We also confirmed LAT1 specific uptake in the tumor and low accumulation in the inflammatory lesion in preclinical studies (J Nucl Med. 2018. vol. 59 no. supplement 1. 1121). The purpose of this study was to evaluate the dosimetry and safety after intravenous administration of 18F-NKO-035 in normal volunteers as a first in human study. Methods: Normal young male volunteers were included in this study (n=4, 21-24 years old, 62-66 kg). After obtaining informed consent and performing screening, subjects were administered with 18F-NKO-035 solutions (221.6 ± 3.8 MBq) and dynamic whole-body PET/CT scans (90 min) were performed. Urine samples were collected until the next day and measured by gamma counter to estimate the radioactivity in the bladder. Time activity curves (TACs) were derived from manually drawn volumes of interest over the following body regions: brain, lungs, heart, liver, kidneys, stomach, pancreas, spleen, lumber spine and urinary bladder contents using PMOD software (ver 3.604). Residence time (hr) was calculated from the area under the curve of each TAC by trapezoidal method with physical decay after the last measurement point. Organ absorbed doses and effective dose (ED) were calculated with OLINDA/EXM 2.0 using the adult male phantom (73.7kg). Safety assessments with interviews, vital signs, laboratory blood / urine tests and electrocardiograms were performed before and one day after 18F-NKO-035 injection. Results: Time activity curves and dynamic PET scans showed low physiological accumulation in major organs except for kidney and urine excretion, reflecting the minimal expression of LAT1 in normal tissues. Highest absorbed dose was observed in the urinary bladder wall (0.302 ± 0.052 mGy/MBq), followed by the kidney (0.053 ± 0.011 mGy/MBq), prostate (0.026 ± 0.003 mGy/MBq) and rectum (0.020 ± 0.002 mGy/MBq). ED was estimated as 4.4 ± 0.39 mSv (0.020 ± 0.002 mSv/MBq), which is within the range of International Commission on Radiological Protection (ICRP) recommendation 2007 (Publication 103) including CT dose (2.33 ± 0.03 mSv). No significant changes were observed in the interviews, vital signs, laboratory blood / urine tests and electrocardiograms after administration of 18F-NKO-035 without any adverse events. Conclusions: This study demonstrated the safety of 18F-NKO-035 injection as well as the favorable whole-body distribution with low accumulation in the normal organs, suggesting the feasibility of tumor specific PET imaging as a LAT1 probe. Further study is warranted to confirm the LAT1 specific uptakes in cancer patients toward the theranostics targeting LAT1. ER -