Synthesis and radiopharmacological characterization of 2β-carbo-2’-[18F]fluoroethoxy-3β-(4-bromo-phenyl)tropane ([18F]MCL-322) as a potential PET radiotracer for imaging the dopamine transporter (DAT)


Synthesis and radiopharmacological characterization of 2β-carbo-2’-[18F]fluoroethoxy-3β-(4-bromo-phenyl)tropane ([18F]MCL-322) as a potential PET radiotracer for imaging the dopamine transporter (DAT)

Wüst, F.; Berndt, M.; Strobel, K.; van den Hoff, J.; Peng, X.; Neumeyer, J. L.; Bergmann, R.

The fluoroalkyl-containing tropane derivative 2β-carbo-2’-fluoroethoxy-3β-(4-bromo-phenyl)tropane (MCL-322) is a highly potent and selective ligand for the dopamine transporter (DAT). The compound was labeled with the short-lived positron emitter 18F in a single step by nucleophilic displacement of the corresponding tosylate precursor MCL-323 with n.c.a. [18F]fluoride. The positron emission tomography (PET) radiotracer 2βcarbo-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 1.6-2.4 Ci/µmol (60-90 GBq/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) 5 min after injection, which increased to 4.2 % ID/g after 60 min. The uptake in the cere¬bellum was 1.8 % ID/g and 0.6 % ID/g after 5 min and 60 min post injection, respectively. Specific binding to DAT of [18F]MCL-322 was confirmed by blocking ex¬periments using the high affinity DAT ligand GBR 12909. The radiopharmacological characterization was completed with metabolite and autoradiographic studies confirming the highly 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.

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