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Initial Human PET Imaging Studies with the Dopamine Transporter Ligand ¹⁸F-FECNT

¹ PET Center, Emory University, Atlanta, Georgia
² Department of Neurology, Emory University, Atlanta, Georgia
³ Department of Radiology, Emory University, Atlanta, Georgia
⁴ Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia
⁵ Department of Anesthesiology, Emory University, Atlanta, Georgia
⁶ Biomedical Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
⁷ Center for Cognitive Neuroscience, Dartmouth College, Hanover, New Hampshire

The aim of this study was to do an initial assessment of the usefulness of 2ß-carbomethoxy-3ß-(4-chlorophenyl)-8-(2-¹⁸F-fluoroethyl)nortropane (¹⁸F-FECNT) PET scanning in determining in vivo brain dopamine transporter (DAT) density in healthy humans and subjects with Parkinson’s disease (PD). Methods: We investigated 6 neurologically healthy subjects and 5 PD patients: 2 with mild unilateral disease, 1 with mild-to-moderate bilateral disease, and 2 with moderately severe bilateral disease. The healthy subjects underwent a 3-h PET scan (26 frames) and the PD subjects underwent a 2-h PET scan (23 frames) while ¹⁸F-FECNT was being injected over the first 5 min of the scan. Arterial blood samples were taken throughout scanning for well-counter and metabolite analysis to determine the presence of possible active metabolites. The scans were reconstructed; then we placed spheric regions of interest in the caudate nuclei, putamena, thalami, brain stem, cerebellum, and occipital cortex of each subject. The radioactivity level in each region was calculated for each frame of a subject’s PET scan. Then we calculated target tissue-to-cerebellum ratios for each time frame. Results: The analysis of arterial blood samples revealed that metabolism of the tracer was rapid. The ether-extractable component of the arterial input was >98% pure ¹⁸F-FECNT. The caudate nucleus and putamen exhibited the highest uptake and prolonged retention of the radioligand. They both attained maximum uptake at 90 min, with the healthy subjects’ average caudate- and putamen-to-cerebellum ratios (±SD) at that time being 9.0 ± 1.2 and 7.8 ± 0.7, respectively. The maximal caudate-to-cerebellum ratios for the healthy subjects ranged from 7.6 to 10.5 and their maximal putamen-to-cerebellum ratios ranged from 7.1 to 9.3. The 2 early-stage, unilateral PD patients had, at 90 min, an average right caudate-to-cerebellum ratio of 5.3 ± 1.1 and a left ratio of 5.9 ± 0.7 and an average right putamen-to cerebellum ratio of 2.8 ± 0.1 and a left ratio of 3.0 ± 0.6. The late-stage PD patients had, at 90 min, an average right caudate-to-cerebellum ratio of 3.7 ± 0.4 and a left ratio of 3.9 ± 0 and an average right putamen-to cerebellum ratio of 1.8 ± 0.1 and a left ratio of 1.8 ± 0. Conclusion: These results indicate that ¹⁸F-FECNT is an excellent candidate radioligand for in vivo imaging of the DAT system in humans. It has a much higher affinity for DAT than for the serotonin transporter and yields the highest peak striatum-to-cerebellum ratios and has among the most favorable kinetics of ¹⁸F-radiolabeled DAT ligands. Having picked up presymptomatic changes in the hemisphere opposite the unaffected side of the body in our early-stage (unilateral) PD patients, it appears that, like other DAT radioligands, it may be able to identify presymptomatic PD.

Key Words: dopamine transporter • PET • 2ß-carbomethoxy-3ß-(4-chlorophenyl)-8-(2-¹⁸F-fluoroethyl)nortropane • Parkinson’s disease

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