Nuclear Science and Techniques

《核技术》(英文版) ISSN 1001-8042 CN 31-1559/TL     2019 Impact factor 1.556

Nuclear Science and Techniques ›› 2009, Vol. 20 ›› Issue (1): 11-16 doi: 10.13538/j.1001-8042/nst.20.11-16

• RADIOCHEMISTRY, RADIOPHARMACEUTICALS AND NUCLEAR MEDICIN • Previous Articles     Next Articles

Animal biodistribution, safety and validation study of dopamine transporter PET imaging agent 18F-FECNT

WANG Songpei1 CHEN Zhengping 1,2,* LI Xiaomin1 TANG Jie1 LIU Chunyi1 ZOU Meifen1 PAN Donghui1 LU Chunxiong1 XU Yuping1 XU Xijie1 ZHOU Xingqin1 JIN Jian2   

  1. 1 The Key Laboratory of Nuclear Medicine, Ministry of Health PRC, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, PR China; 2 School of Medicine and Pharmaceutics, Jiangnan University, Wuxi 214122, PR China
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WANG Songpei, CHEN Zhengping, LI Xiaomin, TANG Jie, LIU Chunyi, ZOU Meifen. Animal biodistribution, safety and validation study of dopamine transporter PET imaging agent 18F-FECNT.Nuclear Science and Techniques, 2009, 20(1): 11-16     doi: 10.13538/j.1001-8042/nst.20.11-16

Abstract:

This work was to investigate the pharmacologic characteristics of 18F-FECNT (2β-carbomethoxy-3β- (4-chlorophenyl)-8-(2-[18F]fluoroethyl)nortropane) as a dopamine transporter (DAT) PET imaging agent. Its partition coefficients were determined in n-octanol and phosphate buffer (PB) (pH 7.0 and pH 7.4). 6-Hydroxydopamine (6-OHDA) left-sided lesioned Parkinsonian rats were established and validated by rotational behavior tests. Biodistribution in vivo in mice, autoradiography in normal and hemi-Parkinsonian rat brains, and toxicity test were performed. The results showed that partition coefficients were 34.14 (pH 7.0) and 56.41 (pH 7.4), respectively. Biodistribution exhibited rapid uptake and favorable retention in the mice brains. The major radioactivity was metabolized by the hepatic system. The autoradiography showed that 18F-FECNT was highly concentrated in striatum, and that the left and the right striatal uptake were symmetrical in normal SD rat brains. In left-sided lesioned PD rat brains, the striatal uptake of 18F-FECNT bilaterally decreased in comparison with normal rats. No significant uptake was visible in the 6-OHDA lesioned-sided striatal areas. The results demonstrated that 18F-FECNT binds to DAT was specific. Toxicity trial displayed that the acceptable dose per kilogram to mice was 625 times greater than that to human. These indicate that 18F-FECNT is a potentially safe and useful DAT PET imaging agent in the brain.

Key words: Dopamine transporter (DAT), PET, 18F-FECNT, Parkinson’s disease (PD), Biodistribution, Autoradiography