Synthesis and radiopharmacological characterization of 2beta-carbo-2'-[18F]fluoroethoxy-3beta-(4-bromo-phenyl)tropane ([18F]MCL-322) as a PET radiotracer for imaging the dopamine transporter (DAT).
Synthesis and radiopharmacological characterization of 2beta-carbo-2'-[18F]fluoroethoxy-3beta-(4-bromo-phenyl)tropane ([18F]MCL-322) as a PET radiotracer for imaging the dopamine transporter (DAT).
复制标题
2β-carbo-2-[18F]氟乙氧基-3β-(4-溴苯基)托烷 ([18F]MCL-322) 的合成和放射性药理学表征，作为 PET 放射性示踪剂用于多巴胺转运蛋白 (DAT) 成像。
DOI：
10.1016/j.bmc.2007.04.019
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发表时间：
2007
影响因子：
3.5
通讯作者：
Bergmann,R
中科院分区：
文献类型：
--
作者：
Wuest,F;Berndt,M;Strobel,K;vandenHoff,J;Peng,X;Neumeyer,JL;Bergmann,R
The fluoroalkyl-containing tropane derivative 2β-carbo-2′-fluoroethoxy-3β-(4-bromo-phenyl)tropane (MCL-322) is a highly potent and moderately selective ligand for the dopamine transporter (DAT). The compound was labeled with the short-lived positron emitter18F in a single step by nucleophilic displacement of the corresponding tosylate precursor MCL-323 with no-carrier-added [18F]fluoride. The positron emission tomography (PET) radiotracer 2β-carbo-2′-[18F]fluoroethoxy-3β-(4-bromo-phenyl)tropane [18F]MCL-322 was obtained in decay-corrected radiochemical yields of 30–40% at a specific radioactivity of 1.6–2.4Ci/μmol (60–90GBq/μmol) at the end-of-synthesis (EOS). Small animal PET, ex vivo and in vivo biodistribution experiments in rats demonstrated a high uptake in the striatum (3.2% ID/g) 5min after injection, which increased to 4.2% ID/g after 60min. The uptake in the cerebellum was 1.8% ID/g and 0.6% ID/g after 5min and 60min post-injection, respectively. Specific binding to DAT of [18F]MCL-322 was confirmed by blocking experiments using the high affinity DAT ligand GBR 12909. The radiopharmacological characterization was completed with metabolite and autoradiographic studies confirming the selective uptake of [18F]MCL-322 in the striatum. It is concluded that the simple single-step radiosynthesis of [18F]MCL-322 and the promising radiopharmacological data make [18F]MCL-322 an attractive candidate for the further development of a PET radiotracer potentially suitable for clinical DAT imaging in the human brain.
