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This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Gao, Y. Articles by Dannals, R. PubMed Articles by Gao, Y. Articles by Dannals, R.

Synthesis, binding affinity and radiosynthesis of [18F]JHU87522, a radioligand with optimal properties for quantitative PET imaging of nicotinic acetylcholine receptors (nAChRs)

¹ Dept. of Radiology, Johns Hopkins University, Baltimore, Maryland; ² Georgetown U., Washington, District of Columbia

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Objectives: The currently available PET radioligands for imaging nAChR in human brain have substantial drawbacks including slow brain kinetics and low binding potentials. The goal of this study was to design, synthesize and characterize an optimal radioligand for in vivo PET imaging of nAChR.

Methods: A series of nAChR ligands were synthesized by multi-step synthesis. In vitro receptor binding assays of the series were performed using rat cortical membranes and stably expressed cell lines of seven nAChR subtypes. The lipophilicity values (logD7.4) were determined experimentally. [18F]JHU86428, [18F]JHU86430 and [18F]JHU87522 were prepared in one step by radiofluorination of corresponding bromo precursors.

Results: We have synthesized a series of nAChR ligands with picomolar binding affinities at cerebral 4β2-nAChR and low binding affinity at ganglionic 3β4-nAChR. The lipophilicity values of the radioligands were in the optimal range for BBB permeability (logD7.4=0.7-1.0). The best ligands of the series ([18F]JHU86428, [18F]JHU86430 and [18F]JHU87522) were radiolabeled in one step with high radiochemical yields (18-41%), specific activities (6300-43000 mCi/µmol) and radiochemical purity (>98%).

Conclusions: Three high affinity nAChR ligands with optimal logD values for BBB permeability have been synthesized. An automated one-step 18F-radiosynthesis for all radioligands has been developed. The best compound of the series, a selective 4β2-nAChR radioligand [18F]JHU87522, exhibited optimally rapid brain kinetics and high binding potentials (see PET studies in Gao et al., this meeting) and holds great promise for quantitative PET imaging study of nAChRs in humans.

Research Support: JHU Radiology, PDSP/NIMH

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Gao, Y. Articles by Dannals, R. PubMed Articles by Gao, Y. Articles by Dannals, R.