Characterisation of [ 11C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter

Patrick J. Riss; Jacob M. Hooker; Colleen Shea; Youwen Xu; Pauline Carter; Donald Warner; Valentina Ferrari; Sung Won Kim; Franklin I. Aigbirhio; Joanna S. Fowler; Frank Roesch

doi:10.1016/j.bmcl.2011.10.053

Characterisation of [ ¹¹C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter

Patrick J. Riss, Jacob M. Hooker, Colleen Shea, Youwen Xu, Pauline Carter, Donald Warner, Valentina Ferrari, Sung Won Kim, Franklin I. Aigbirhio, Joanna S. Fowler, Frank Roesch

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

N-(4-fluorobut-2-yn-1-yl)-2β-carbomethoxy-3β-(4′-tolyl) nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [ ¹¹C]PR04.MZ ([ ¹¹C]-1) has been developed using GMP compliant equipment. An adult female Papio anubis baboon was studied using a test-retest protocol with [ ¹¹C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (f _P), plasma input functions and metabolic degradation of the radiotracer [ ¹¹C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (V _T) and non-displaceable binding potentials (BP _ND) for various brain regions and the blood were obtained from kinetic modelling. [ ¹¹C]-1 shows promising results as a selective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man.

Original language	English
Pages (from-to)	679-682
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2011.10.053
State	Published - 1 Jan 2012
Externally published	Yes

Keywords

Carbon-11
Dopamine transporter
Non-human primates
PET imaging

Access to Document

10.1016/j.bmcl.2011.10.053

Cite this

Riss, P. J., Hooker, J. M., Shea, C., Xu, Y., Carter, P., Warner, D., Ferrari, V., Kim, S. W., Aigbirhio, F. I., Fowler, J. S., & Roesch, F. (2012). Characterisation of [ ¹¹C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter. Bioorganic and Medicinal Chemistry Letters, 22(1), 679-682. https://doi.org/10.1016/j.bmcl.2011.10.053

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title = "Characterisation of [ 11C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter",

abstract = "N-(4-fluorobut-2-yn-1-yl)-2β-carbomethoxy-3β-(4′-tolyl) nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [ 11C]PR04.MZ ([ 11C]-1) has been developed using GMP compliant equipment. An adult female Papio anubis baboon was studied using a test-retest protocol with [ 11C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (f P), plasma input functions and metabolic degradation of the radiotracer [ 11C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (V T) and non-displaceable binding potentials (BP ND) for various brain regions and the blood were obtained from kinetic modelling. [ 11C]-1 shows promising results as a selective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man.",

keywords = "Carbon-11, Dopamine transporter, Non-human primates, PET imaging",

author = "Riss, \{Patrick J.\} and Hooker, \{Jacob M.\} and Colleen Shea and Youwen Xu and Pauline Carter and Donald Warner and Valentina Ferrari and Kim, \{Sung Won\} and Aigbirhio, \{Franklin I.\} and Fowler, \{Joanna S.\} and Frank Roesch",

note = "Funding Information: This work was supported by the DFG [Ro 985/21], the US DoE and the Fonds der Chemischen Industrie. ",

year = "2012",

month = jan,

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doi = "10.1016/j.bmcl.2011.10.053",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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Riss, PJ, Hooker, JM, Shea, C, Xu, Y, Carter, P, Warner, D, Ferrari, V, Kim, SW, Aigbirhio, FI, Fowler, JS & Roesch, F 2012, 'Characterisation of [ ¹¹C]PR04.MZ in Papio anubis baboon: A selective high-affinity radioligand for quantitative imaging of the dopamine transporter', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 1, pp. 679-682. https://doi.org/10.1016/j.bmcl.2011.10.053

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T1 - Characterisation of [ 11C]PR04.MZ in Papio anubis baboon

T2 - A selective high-affinity radioligand for quantitative imaging of the dopamine transporter

AU - Riss, Patrick J.

AU - Hooker, Jacob M.

AU - Shea, Colleen

AU - Xu, Youwen

AU - Carter, Pauline

AU - Warner, Donald

AU - Ferrari, Valentina

AU - Kim, Sung Won

AU - Aigbirhio, Franklin I.

AU - Fowler, Joanna S.

AU - Roesch, Frank

N1 - Funding Information: This work was supported by the DFG [Ro 985/21], the US DoE and the Fonds der Chemischen Industrie.

PY - 2012/1/1

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N2 - N-(4-fluorobut-2-yn-1-yl)-2β-carbomethoxy-3β-(4′-tolyl) nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [ 11C]PR04.MZ ([ 11C]-1) has been developed using GMP compliant equipment. An adult female Papio anubis baboon was studied using a test-retest protocol with [ 11C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (f P), plasma input functions and metabolic degradation of the radiotracer [ 11C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (V T) and non-displaceable binding potentials (BP ND) for various brain regions and the blood were obtained from kinetic modelling. [ 11C]-1 shows promising results as a selective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man.

AB - N-(4-fluorobut-2-yn-1-yl)-2β-carbomethoxy-3β-(4′-tolyl) nortropane (PR04.MZ, 1) is a PET radioligand for the non-invasive exploration of the function of the cerebral dopamine transporter (DAT). A reliable automated process for routine production of the carbon-11 labelled analogue [ 11C]PR04.MZ ([ 11C]-1) has been developed using GMP compliant equipment. An adult female Papio anubis baboon was studied using a test-retest protocol with [ 11C]-1 in order to assess test-retest reliability, metabolism and CNS distribution profile of the tracer in non-human primates. Blood sampling was performed throughout the studies for determination of the free fraction in plasma (f P), plasma input functions and metabolic degradation of the radiotracer [ 11C]-1. Time-activity curves were derived for the putamen, the caudate nucleus, the ventral striatum, the midbrain and the cerebellum. Distribution volumes (V T) and non-displaceable binding potentials (BP ND) for various brain regions and the blood were obtained from kinetic modelling. [ 11C]-1 shows promising results as a selective marker of the presynaptic dopamine transporter. With the reliable visualisation of the extra-striatal dopaminergic neurons and no indication on labelled metabolites, the tracer provides excellent potential for translation into man.

KW - Carbon-11

KW - Dopamine transporter

KW - Non-human primates

KW - PET imaging

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