Biodistribution and Radiation Dosimetry for the Tau Tracer18F-THK-5351 in Healthy Human Subjects.
18F-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 of18F-THK-5351 in humans and to compare the clinical radiation dosimetry results to estimations published previously with preclinical data.Methods:Serial whole-body PET/CT imaging was performed for 240 min on 12 healthy volunteers after injecting18F-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 normalized18F-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.Results:Overall, the18F-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.Conclusion:Our results suggest that a routine injection of 370 MBq of18F-THK-5351 would lead to an estimated effective dose of 8.4 mSv; hence,18F-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.
Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.|Neuroscience Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Ing-Tsung
IT
Hsiao
Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.|Neuroscience Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Kun-Ju
KJ
Lin
Department of Neurology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
Kuo-Lun
KL
Huang
Department of Neurology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
Chin-Chang
CC
Huang
Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.
Han-Shiuan
HS
Chen
Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.
Shiaw-Pyng
SP
Wey
Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Healthy Aging Research Center and Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.|Neuroscience Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Tzu-Chen
TC
Yen
Division of Neuroimaging, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan.|Department of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan; and.
Nobuyuki
N
Okamura
Department of Neurology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan tulu@ms36.hinet.net.|Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan.
Jung-Lung
JL
Hsu
D000328:Adult; D000631:Aminopyridines / Q000493:pharmacokinetics*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011804:Quinolines / Q000493:pharmacokinetics*; D011849:Radioactive Tracers; D011874:Radiometry; D012984:Software; D014018:Tissue Distribution; D016875:tau Proteins / Q000378:metabolism*
D000631:Aminopyridines; D011804:Quinolines; D011849:Radioactive Tracers; C000608225:THK5351; D016875:tau Proteins
18F-THK-5351; Alzheimer’s disease; radiation dosimetry; tau; whole body biodistribution