Biodistribution and Radiation Dosimetry for the Tau Tracer 18 F-THK-5351 in Healthy Human Subjects

• Published in: Journal of Nuclear Medicine Vol. 58; no. 9; pp. 1498 - 1503
• Main Authors: Hsiao, Ing-Tsung, Lin, Kun-Ju, Huang, Kuo-Lun, Huang, Chin-Chang, Chen, Han-Shiuan, Wey, Shiaw-Pyng, Yen, Tzu-Chen, Okamura, Nobuyuki, Hsu, Jung-Lung
• Format: Journal Article
• Language: English
• Published: United States 01.09.2017
• Subjects: Adult; Aminopyridines - pharmacokinetics; Female; Healthy Volunteers; Humans; Male; Middle Aged; Positron-Emission Tomography; Quinolines - pharmacokinetics; Radioactive Tracers; Radiometry; Software; tau Proteins - metabolism; Tissue Distribution; 18F-THK-5351; tau; whole body biodistribution; Alzheimer’s disease; radiation dosimetry
• ISSN: 0161-5505; 2159-662X; 1535-5667
• DOI: 10.2967/jnumed.116.189126

F-THK-5351 is a novel radiotracer that demonstrates high binding selectivity and affinity for tau pathology and exhibits better pharmacokinetics in the living brain than previous THK tau probes. The aim of the present study was to estimate the radiation dose of F-THK-5351 in humans and to compare the clinical radiation dosimetry results to estimations published previously with preclinical data. Serial whole-body PET/CT imaging was performed for 240 min on 12 healthy volunteers after injecting F-THK-5351 (mean administered activity, 377.8 ± 14.0 MBq; range, 340-397 MBq). The bladder and gallbladder were delineated on PET images, and the other organs were delineated on CT images. Voided urine activity was recorded. The decay-corrected and normalized F-THK-5351 activity of 15 source-organ regions as a function of time was entered into the OLINDA/EXM software to calculate the effective dose for each subject following the medical internal radiation dosimetry schema. Overall, the F-THK-5351 injection was well tolerated. The highest mean initial uptake at 10 min after injection was in the liver (11.4% ± 2.0%), lung (5.7% ± 2.1%), intestine (3.4% ± 0.8%), and kidney (1.4% ± 0.3%). The highest mean absorbed dose of radiation was in the gallbladder wall (242.2 ± 105.2 μGy/MBq), upper large intestine (90.0 ± 15.8 μGy/MBq), small intestine (79.5 ± 13.8 μGy/MBq), and liver (55.8 ± 6.1 μGy/MBq). The resultant whole-body effective dose was 22.7 ± 1.3 μSv/MBq. Our results suggest that a routine injection of 370 MBq of F-THK-5351 would lead to an estimated effective dose of 8.4 mSv; hence, F-THK-5351 has a radiation burden similar to that of other commonly used clinical tracers. Our findings in humans were compatible with recently published preclinical dosimetry data extrapolated from mice.