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

RADIOCHEMISTRY, RADIOPHARMACEUTICALS AND NUCLEAR MEDICINE

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

WANG Songpei，

CHEN Zhengping，

LI Xiaomin，

TANG Jie，

LIU Chunyi，

ZOU Meifen，

PAN Donghui，

LU Chunxiong，

XU Yuping，

XU Xijie，

ZHOU Xingqin，

JIN Jian

Nuclear Science and Techniques

Vol.20, No.1

pp.11-16

Published in print 20 Feb 2009

DOI：10.13538/j.1001-8042/nst.20.11-16

32900

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.

Dopamine transporter (DAT)PET18F-FECNTParkinson's disease (PD)BiodistributionAutoradiography

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