title: Optimization and Biodistribution of [(11)C]-TKF, An Analog of Tau Protein Imaging Agent [(18)F]-THK523.
abstract: The quantification of neurofibrillary tangles (NFTs) using specific PET tracers can facilitate the diagnosis of Alzheimer's disease (AD) and allow monitoring of disease progression and treatment efficacy. [(18)F]-THK523 has shown high affinity and selectivity for tau pathology. However, its high retention in white matter, which makes simple visual inspection difficult, may limit its use in research or clinical settings. In this paper, we optimized the automated radiosynthesis of [(11)C]-TKF and evaluated its biodistribution and toxicity in C57 mice. [(11)C]-TKF can be made by reaction precursor with [(11)C]MeOTf or (11)CH₃I, but [(11)C]MeOTf will give us higher labeling yields and specific activity. [(11)C]-TKF presented better brain uptake in normal mouse than [(18)F]-THK523 (3.23% ± 1.25% ID·g(-1) vs. 2.62% ± 0.39% ID·g(-1) at 2 min post-injection). The acute toxicity studies of [(11)C]-TKF were unremarkable.
authors.affiliation: PET Center, Huashan Hospital, Fudan University, Shanghai 200235, China. karenyanyan@hotmail.com.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Kong
authors.affiliation: PET Center, Huashan Hospital, Fudan University, Shanghai 200235, China. guanyihui@hotmail.com.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Guan
authors.affiliation: PET Center, Huashan Hospital, Fudan University, Shanghai 200235, China. fengchun_hua@163.com.
authors.forename: Fengchun
authors.initials: F
authors.lastname: Hua
authors.affiliation: PET Center, Huashan Hospital, Fudan University, Shanghai 200235, China. pet_111@126.com.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: PET Center, Huashan Hospital, Fudan University, Shanghai 200235, China. xiuhong_lu2015@sina.com.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200030, China. tengfangzhufdu@gmail.com.
authors.forename: Tengfang
authors.initials: T
authors.lastname: Zhu
authors.affiliation: No.6 Shanghai People's Hospital, Jiaotong University, Shanghai 200235, China. bizeng_zhao@sina.com.
authors.forename: Bizeng
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai 201203, China. zhujianhua_fudan@126.com.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai 201203, China. congliphar@126.com.
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai 201203, China. chenjian_david@yeah.net.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D016875:tau Proteins
keywords: Alzheimer’s disease; imaging; neurofibrillary tangles (NFTs); positron emission tomography (PET); tau