HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zoghbi, S. S. Articles by Innis, R. B. Search for Related Content PubMed PubMed Citation Articles by Zoghbi, S. S. Articles by Innis, R. B.

PET Imaging of the Dopamine Transporter with ¹⁸F-FECNT: A Polar Radiometabolite Confounds Brain Radioligand Measurements

Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland

Correspondence: For correspondence or reprints contact: Sami S. Zoghbi, PhD, Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, 1 Center Dr., Room B3-10, MS 0135, Bethesda, MD 20892-0135. E-mail: zoghbis{at}mail.nih.gov

¹⁸F-2ß-Carbomethoxy-3ß-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (¹⁸F-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. Methods: Two rats were infused with ¹⁸F-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography–mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with ¹⁸F-FECNT and scanned kinetically, with serial arterial blood analysis. Results: At 60 min after the injection of rats, ¹⁸F-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-dealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was ¹⁸F-fluoroacetaldehyde, the product expected from the N-dealkylation of ¹⁸F-FECNT, or its oxidation product, ¹⁸F-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 ± 0.1-fold (mean ± SD; n = 3) in nonhuman primates between 60 and 240 min after injection. Conclusion: An ¹⁸F-fluoroalkyl metabolite of ¹⁸F-FECNT originating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of ¹⁸F-FECNT will be prone to more errors than analysis with a measured arterial input function.

Key Words: in vivo metabolism • dopamine transporter • receptor • ¹⁸F-2ß-carbomethoxy-3ß-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane

Related articles in JNM:

This Month in JNM

JNM 2006 47: 7a-8a. [Full Text]  

This article has been cited by other articles:

				G. E. Terry, J. Hirvonen, J.-S. Liow, S. S. Zoghbi, R. Gladding, J. T. Tauscher, J. M. Schaus, L. Phebus, C. C. Felder, C. L. Morse, et al. Imaging and Quantitation of Cannabinoid CB1 Receptors in Human and Monkey Brains Using 18F-Labeled Inverse Agonist Radioligands J. Nucl. Med., January 1, 2010; 51(1): 112 - 120. [Abstract] [Full Text] [PDF]

				Y. Fujimura, S. S. Zoghbi, F. G. Simeon, A. Taku, V. W. Pike, R. B. Innis, and M. Fujita Quantification of Translocator Protein (18 kDa) in the Human Brain with PET and a Novel Radioligand, 18F-PBR06 J. Nucl. Med., July 1, 2009; 50(7): 1047 - 1053. [Abstract] [Full Text] [PDF]

				N. Seneca, S. S. Zoghbi, J.-S. Liow, W. Kreisl, P. Herscovitch, K. Jenko, R. L. Gladding, A. Taku, V. W. Pike, and R. B. Innis Human Brain Imaging and Radiation Dosimetry of 11C-N-Desmethyl-Loperamide, a PET Radiotracer to Measure the Function of P-Glycoprotein J. Nucl. Med., May 1, 2009; 50(5): 807 - 813. [Abstract] [Full Text] [PDF]

				T. Itoh, K. Abe, S. S. Zoghbi, O. Inoue, J. Hong, M. Imaizumi, V. W. Pike, R. B. Innis, and M. Fujita PET Measurement of the In Vivo Affinity of 11C-(R)-Rolipram and the Density of Its Target, Phosphodiesterase-4, in the Brains of Conscious and Anesthetized Rats J. Nucl. Med., May 1, 2009; 50(5): 749 - 756. [Abstract] [Full Text] [PDF]

				S. S. Zoghbi, J.-S. Liow, F. Yasuno, J. Hong, E. Tuan, N. Lazarova, R. L. Gladding, V. W. Pike, and R. B. Innis 11C-Loperamide and Its N-Desmethyl Radiometabolite Are Avid Substrates for Brain Permeability-Glycoprotein Efflux J. Nucl. Med., April 1, 2008; 49(4): 649 - 656. [Abstract] [Full Text] [PDF]