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

@article{f67cbc85cf6f4a0caa7bc25fdc13eef5,

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,

day = "1",

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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