Portal de Periódicos da CAPES

Altropane, a SPECT or PET imaging probe for dopamine neurons: I. dopamine transporter binding in primate brain

1998; Wiley; Volume: 29; Issue: 2 Linguagem: Inglês

10.1002/(sici)1098-2396(199806)29

1098-2396

Bertha K. Madras, Peter C. Meltzer, Anna Y. Liang, David R. Elmaleh, John W. Babich, Alan J. Fischman,

Advanced MRI Techniques and Applications

SynapseVolume 29, Issue 2 p. 93-104 Altropane, a SPECT or PET imaging probe for dopamine neurons: I. dopamine transporter binding in primate brain Bertha K. Madras, Corresponding Author Bertha K. Madras [email protected] Department of Psychiatry, Harvard Medical School, New England Regional Primate Research Center, Southborough, MassachusettsDr. Bertha K. Madras, Harvard Medical School, New England Regional Primate Research Center, 1 Pine Hill Drive, Southborough, MA 01772-9102Search for more papers by this authorPeter C. Meltzer, Peter C. Meltzer Organix Inc., Woburn, MassachusettsSearch for more papers by this authorAnna Y. Liang, Anna Y. Liang Organix Inc., Woburn, MassachusettsSearch for more papers by this authorDavid R. Elmaleh, David R. Elmaleh Department of Radiology, Massachusetts General Hospital, Boston, MassachusettsSearch for more papers by this authorJohn Babich, John Babich Department of Radiology, Massachusetts General Hospital, Boston, MassachusettsSearch for more papers by this authorAlan J. Fischman, Alan J. Fischman Department of Radiology, Massachusetts General Hospital, Boston, MassachusettsSearch for more papers by this author Bertha K. Madras, Corresponding Author Bertha K. Madras [email protected] Department of Psychiatry, Harvard Medical School, New England Regional Primate Research Center, Southborough, MassachusettsDr. Bertha K. Madras, Harvard Medical School, New England Regional Primate Research Center, 1 Pine Hill Drive, Southborough, MA 01772-9102Search for more papers by this authorPeter C. Meltzer, Peter C. Meltzer Organix Inc., Woburn, MassachusettsSearch for more papers by this authorAnna Y. Liang, Anna Y. Liang Organix Inc., Woburn, MassachusettsSearch for more papers by this authorDavid R. Elmaleh, David R. Elmaleh Department of Radiology, Massachusetts General Hospital, Boston, MassachusettsSearch for more papers by this authorJohn Babich, John Babich Department of Radiology, Massachusetts General Hospital, Boston, MassachusettsSearch for more papers by this authorAlan J. Fischman, Alan J. Fischman Department of Radiology, Massachusetts General Hospital, Boston, MassachusettsSearch for more papers by this author First published: 07 December 1998 https://doi.org/10.1002/(SICI)1098-2396(199806)29:2 3.0.CO;2-5Citations: 27AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Increasing evidence suggests that the dopamine transporter is an important marker for physiological and pathological changes in dopamine neurons. Potent dopamine transport inhibitors of the phenyltropane series (e.g., WIN 35,428 or CFT) are particularly suitable for PET (positron emission tomography) or SPECT (single photon emission computed tomography) imaging of the dopamine transporter in living brain. We investigated whether altropane, an N-iodoallyl analog of WIN 35,428 (IACFT:E-N-iodoallyl-2β-carbomethoxy-3β-(4-fluorophenyl)tropane), displayed in vitro properties suitable for evaluation as a SPECT imaging agent. In brain striatum of cynomolgus monkey (Macaca fascicularis), the unlabeled E-isomer (IC50: 6.62 ± 0.78 nM) was more potent than the Z-isomer (IC50: 52.6 ± 0.3 nM) and displayed a relatively high dopamine:serotonin transporter selectivity (28-fold). In radiolabeled form, [125I]altropane bound to sites in the striatum with a single high affinity (KD: 5.33 ± 0.55 nM) and with a site density (BMAX: 301 pmol/g original wet tissue weight) that was within the density range reported previously for the dopamine transporter in striatum. Drugs inhibited [125I]altropane binding with a rank order of potency that corresponded closely to their potencies for inhibiting [3H]WIN 35,428 binding (r2: 0.99; P < 0.0001) to the blocking dopamine transport. The favorable binding properties of altropane, together with its rapid entry into primate brain and highly localized distribution in dopamine-rich brain regions, suggest it is a suitable iodinated probe for monitoring the dopamine transporter in vitro and in vivo by SPECT or PET imaging. Synapse 29:93–104, 1998. © 1998 Wiley-Liss, Inc. Citing Literature Volume29, Issue2June 1998Pages 93-104 RelatedInformation