Dopamine transporter binding in rat striatum

a comparison of [O-methyl-11C]β-CFT and [N-methyl-11C]β-CFT

Karmen Yoder, Gary Hutchins, Bruce H. Mock, Xiangshu Fei, Wendy L. Winkle, Bruce D. Gitter, Paul Territo, Qi-Huang Zheng

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Introduction: Positron emission tomography scanning with radiolabeled phenyltropane cocaine analogs is important for quantifying the in vivo density of monoamine transporters, including the dopamine transporter (DAT). [11C]β-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [11C]β-CFT is commonly labeled at the N-methyl position. However, labeling of [11C]β-CFT at the O-methyl position is a simpler procedure and results in a shorter synthesis time [desirable in small-animal studies, where specific activity (SA) is crucial]. In this study, we sought to validate that the O-methylated form of [11C]β-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form. Methods: Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-11C]β-CFT and once with [O-methyl-11C]β-CFT. DAT binding potentials (BP≡B′avail/Kd) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function. Results: [N-Methyl-11C]β-CFT and [O-methyl-11C]β-CFT were synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical purity was >99%. SA at end of bombardment was 258±30 GBq/μmol. Average BP values for right and left striata with [N-methyl-11C]β-CFT were 1.16±0.08 and 1.23±0.14, respectively. BP values for [O-methyl-11C]β-CFT were 1.18±0.08 (right) and 1.22±0.16 (left). Paired t tests demonstrated that labeling position did not affect striatal DAT BP. Conclusions: These results suggest that [O-methyl-11C]β-CFT is quantitatively equivalent to [N-methyl-11C]β-CFT in the rat striatum.

Original languageEnglish
Pages (from-to)11-16
Number of pages6
JournalNuclear Medicine and Biology
Volume36
Issue number1
DOIs
StatePublished - Jan 2009

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Dopamine Plasma Membrane Transport Proteins
Corpus Striatum
Nervous System Diseases
Least-Squares Analysis
Cocaine
Positron-Emission Tomography
Cerebellum
Sprague Dawley Rats
Psychiatry
Animal Models
High Pressure Liquid Chromatography

Keywords

  • [C]β-CFT
  • Animal models
  • Dopamine
  • Dopamine transporter
  • Positron emission tomography
  • Striatum

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Dopamine transporter binding in rat striatum : a comparison of [O-methyl-11C]β-CFT and [N-methyl-11C]β-CFT. / Yoder, Karmen; Hutchins, Gary; Mock, Bruce H.; Fei, Xiangshu; Winkle, Wendy L.; Gitter, Bruce D.; Territo, Paul; Zheng, Qi-Huang.

In: Nuclear Medicine and Biology, Vol. 36, No. 1, 01.2009, p. 11-16.

Research output: Contribution to journalArticle

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abstract = "Introduction: Positron emission tomography scanning with radiolabeled phenyltropane cocaine analogs is important for quantifying the in vivo density of monoamine transporters, including the dopamine transporter (DAT). [11C]β-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [11C]β-CFT is commonly labeled at the N-methyl position. However, labeling of [11C]β-CFT at the O-methyl position is a simpler procedure and results in a shorter synthesis time [desirable in small-animal studies, where specific activity (SA) is crucial]. In this study, we sought to validate that the O-methylated form of [11C]β-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form. Methods: Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-11C]β-CFT and once with [O-methyl-11C]β-CFT. DAT binding potentials (BP≡B′avail/Kd) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function. Results: [N-Methyl-11C]β-CFT and [O-methyl-11C]β-CFT were synthesized with 40-50{\%} radiochemical yields (HPLC purification). Radiochemical purity was >99{\%}. SA at end of bombardment was 258±30 GBq/μmol. Average BP values for right and left striata with [N-methyl-11C]β-CFT were 1.16±0.08 and 1.23±0.14, respectively. BP values for [O-methyl-11C]β-CFT were 1.18±0.08 (right) and 1.22±0.16 (left). Paired t tests demonstrated that labeling position did not affect striatal DAT BP. Conclusions: These results suggest that [O-methyl-11C]β-CFT is quantitatively equivalent to [N-methyl-11C]β-CFT in the rat striatum.",
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AU - Mock, Bruce H.

AU - Fei, Xiangshu

AU - Winkle, Wendy L.

AU - Gitter, Bruce D.

AU - Territo, Paul

AU - Zheng, Qi-Huang

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N2 - Introduction: Positron emission tomography scanning with radiolabeled phenyltropane cocaine analogs is important for quantifying the in vivo density of monoamine transporters, including the dopamine transporter (DAT). [11C]β-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [11C]β-CFT is commonly labeled at the N-methyl position. However, labeling of [11C]β-CFT at the O-methyl position is a simpler procedure and results in a shorter synthesis time [desirable in small-animal studies, where specific activity (SA) is crucial]. In this study, we sought to validate that the O-methylated form of [11C]β-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form. Methods: Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-11C]β-CFT and once with [O-methyl-11C]β-CFT. DAT binding potentials (BP≡B′avail/Kd) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function. Results: [N-Methyl-11C]β-CFT and [O-methyl-11C]β-CFT were synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical purity was >99%. SA at end of bombardment was 258±30 GBq/μmol. Average BP values for right and left striata with [N-methyl-11C]β-CFT were 1.16±0.08 and 1.23±0.14, respectively. BP values for [O-methyl-11C]β-CFT were 1.18±0.08 (right) and 1.22±0.16 (left). Paired t tests demonstrated that labeling position did not affect striatal DAT BP. Conclusions: These results suggest that [O-methyl-11C]β-CFT is quantitatively equivalent to [N-methyl-11C]β-CFT in the rat striatum.

AB - Introduction: Positron emission tomography scanning with radiolabeled phenyltropane cocaine analogs is important for quantifying the in vivo density of monoamine transporters, including the dopamine transporter (DAT). [11C]β-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [11C]β-CFT is commonly labeled at the N-methyl position. However, labeling of [11C]β-CFT at the O-methyl position is a simpler procedure and results in a shorter synthesis time [desirable in small-animal studies, where specific activity (SA) is crucial]. In this study, we sought to validate that the O-methylated form of [11C]β-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form. Methods: Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-11C]β-CFT and once with [O-methyl-11C]β-CFT. DAT binding potentials (BP≡B′avail/Kd) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function. Results: [N-Methyl-11C]β-CFT and [O-methyl-11C]β-CFT were synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical purity was >99%. SA at end of bombardment was 258±30 GBq/μmol. Average BP values for right and left striata with [N-methyl-11C]β-CFT were 1.16±0.08 and 1.23±0.14, respectively. BP values for [O-methyl-11C]β-CFT were 1.18±0.08 (right) and 1.22±0.16 (left). Paired t tests demonstrated that labeling position did not affect striatal DAT BP. Conclusions: These results suggest that [O-methyl-11C]β-CFT is quantitatively equivalent to [N-methyl-11C]β-CFT in the rat striatum.

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KW - Striatum

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