Quantitative analysis of (-)-N-11C-propyl-norapomorphine in vivo binding in nonhuman primates

Dah Ren Hwang, Rajesh Narendran, Yiyun Huang, Mark Slifstein, Peter S. Talbot, Yasuhiko Sudo, Bart N. Van Berckel, Lawrence S. Kegeles, Diana Martinez, Marc Laruelle

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

(-)-N-11C-propyl-norapomorphine (11C-NPA) is a new dopamine agonist PET radiotracer that holds potential for imaging the high-affinity states of dopamine D2-like receptors in the living brain. The goal of this study was to develop and evaluate analytic strategies to derive in vivo 11C-NPA binding parameters. Methods: Two baboons were scanned 4 times after 11C-NPA injections. The metabolite-corrected arterial input functions were measured. Regional brain time-activity curves were analyzed with kinetic and graphical analyses, using the arterial time-activity curve as the input function. Data were also analyzed with the simplified reference-tissue model (SRTM) and graphical analysis with reference-region input. Results: 11C-NPA exhibited moderately fast metabolism, with 31% ± 5% of arterial plasma concentration corresponding to the parent compound at 40 min after injection. Plasma clearance was 29 ± 1 L/h, and plasma free fraction (f1) was 5% ± 1%. For kinetic analysis, a 1-tissue compartment model (1TCM) provided a good fit to the data and more robust derivations of the tissue distribution volumes (VT, in mL/g) than a 2-tissue compartment model (2TCM). Using 1TCM, VTs in the cerebellum and striatum were 3.4 ± 0.4 and 7.5 ± 2 mL/g, respectively, which led to estimates of striatal binding potential (BP) of 4.0 ± 1.1 mL/g and striatal equilibrium specific-to-nonspecific partition coefficient (V3″) of 1.2 ± 0.2. VT values derived with graphical analysis were well correlated with but slightly lower than VT values derived with kinetic analysis. V3″ values derived with SRTM were well correlated with but slightly higher than V3″ values derived with kinetic analysis. Using any method, a significant difference was detected in BP and V3″ values between the 2 animals. It was determined that 30 min of scanning data were sufficient to derive V3″ values using kinetic, graphical (arterial input and reference-region input), and SRTM analyses. Conclusion: This study indicates that 11C-NPA is a suitable PET tracer to quantify the agonist high-affinity sites of D2-like receptors.

Original languageEnglish
Pages (from-to)338-346
Number of pages9
JournalJournal of Nuclear Medicine
Volume45
Issue number2
Publication statusPublished - 1 Feb 2004

Cite this

Hwang, D. R., Narendran, R., Huang, Y., Slifstein, M., Talbot, P. S., Sudo, Y., ... Laruelle, M. (2004). Quantitative analysis of (-)-N-11C-propyl-norapomorphine in vivo binding in nonhuman primates. Journal of Nuclear Medicine, 45(2), 338-346.
Hwang, Dah Ren ; Narendran, Rajesh ; Huang, Yiyun ; Slifstein, Mark ; Talbot, Peter S. ; Sudo, Yasuhiko ; Van Berckel, Bart N. ; Kegeles, Lawrence S. ; Martinez, Diana ; Laruelle, Marc. / Quantitative analysis of (-)-N-11C-propyl-norapomorphine in vivo binding in nonhuman primates. In: Journal of Nuclear Medicine. 2004 ; Vol. 45, No. 2. pp. 338-346.
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abstract = "(-)-N-11C-propyl-norapomorphine (11C-NPA) is a new dopamine agonist PET radiotracer that holds potential for imaging the high-affinity states of dopamine D2-like receptors in the living brain. The goal of this study was to develop and evaluate analytic strategies to derive in vivo 11C-NPA binding parameters. Methods: Two baboons were scanned 4 times after 11C-NPA injections. The metabolite-corrected arterial input functions were measured. Regional brain time-activity curves were analyzed with kinetic and graphical analyses, using the arterial time-activity curve as the input function. Data were also analyzed with the simplified reference-tissue model (SRTM) and graphical analysis with reference-region input. Results: 11C-NPA exhibited moderately fast metabolism, with 31{\%} ± 5{\%} of arterial plasma concentration corresponding to the parent compound at 40 min after injection. Plasma clearance was 29 ± 1 L/h, and plasma free fraction (f1) was 5{\%} ± 1{\%}. For kinetic analysis, a 1-tissue compartment model (1TCM) provided a good fit to the data and more robust derivations of the tissue distribution volumes (VT, in mL/g) than a 2-tissue compartment model (2TCM). Using 1TCM, VTs in the cerebellum and striatum were 3.4 ± 0.4 and 7.5 ± 2 mL/g, respectively, which led to estimates of striatal binding potential (BP) of 4.0 ± 1.1 mL/g and striatal equilibrium specific-to-nonspecific partition coefficient (V3″) of 1.2 ± 0.2. VT values derived with graphical analysis were well correlated with but slightly lower than VT values derived with kinetic analysis. V3″ values derived with SRTM were well correlated with but slightly higher than V3″ values derived with kinetic analysis. Using any method, a significant difference was detected in BP and V3″ values between the 2 animals. It was determined that 30 min of scanning data were sufficient to derive V3″ values using kinetic, graphical (arterial input and reference-region input), and SRTM analyses. Conclusion: This study indicates that 11C-NPA is a suitable PET tracer to quantify the agonist high-affinity sites of D2-like receptors.",
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author = "Hwang, {Dah Ren} and Rajesh Narendran and Yiyun Huang and Mark Slifstein and Talbot, {Peter S.} and Yasuhiko Sudo and {Van Berckel}, {Bart N.} and Kegeles, {Lawrence S.} and Diana Martinez and Marc Laruelle",
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Hwang, DR, Narendran, R, Huang, Y, Slifstein, M, Talbot, PS, Sudo, Y, Van Berckel, BN, Kegeles, LS, Martinez, D & Laruelle, M 2004, 'Quantitative analysis of (-)-N-11C-propyl-norapomorphine in vivo binding in nonhuman primates' Journal of Nuclear Medicine, vol. 45, no. 2, pp. 338-346.

Quantitative analysis of (-)-N-11C-propyl-norapomorphine in vivo binding in nonhuman primates. / Hwang, Dah Ren; Narendran, Rajesh; Huang, Yiyun; Slifstein, Mark; Talbot, Peter S.; Sudo, Yasuhiko; Van Berckel, Bart N.; Kegeles, Lawrence S.; Martinez, Diana; Laruelle, Marc.

In: Journal of Nuclear Medicine, Vol. 45, No. 2, 01.02.2004, p. 338-346.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Quantitative analysis of (-)-N-11C-propyl-norapomorphine in vivo binding in nonhuman primates

AU - Hwang, Dah Ren

AU - Narendran, Rajesh

AU - Huang, Yiyun

AU - Slifstein, Mark

AU - Talbot, Peter S.

AU - Sudo, Yasuhiko

AU - Van Berckel, Bart N.

AU - Kegeles, Lawrence S.

AU - Martinez, Diana

AU - Laruelle, Marc

PY - 2004/2/1

Y1 - 2004/2/1

N2 - (-)-N-11C-propyl-norapomorphine (11C-NPA) is a new dopamine agonist PET radiotracer that holds potential for imaging the high-affinity states of dopamine D2-like receptors in the living brain. The goal of this study was to develop and evaluate analytic strategies to derive in vivo 11C-NPA binding parameters. Methods: Two baboons were scanned 4 times after 11C-NPA injections. The metabolite-corrected arterial input functions were measured. Regional brain time-activity curves were analyzed with kinetic and graphical analyses, using the arterial time-activity curve as the input function. Data were also analyzed with the simplified reference-tissue model (SRTM) and graphical analysis with reference-region input. Results: 11C-NPA exhibited moderately fast metabolism, with 31% ± 5% of arterial plasma concentration corresponding to the parent compound at 40 min after injection. Plasma clearance was 29 ± 1 L/h, and plasma free fraction (f1) was 5% ± 1%. For kinetic analysis, a 1-tissue compartment model (1TCM) provided a good fit to the data and more robust derivations of the tissue distribution volumes (VT, in mL/g) than a 2-tissue compartment model (2TCM). Using 1TCM, VTs in the cerebellum and striatum were 3.4 ± 0.4 and 7.5 ± 2 mL/g, respectively, which led to estimates of striatal binding potential (BP) of 4.0 ± 1.1 mL/g and striatal equilibrium specific-to-nonspecific partition coefficient (V3″) of 1.2 ± 0.2. VT values derived with graphical analysis were well correlated with but slightly lower than VT values derived with kinetic analysis. V3″ values derived with SRTM were well correlated with but slightly higher than V3″ values derived with kinetic analysis. Using any method, a significant difference was detected in BP and V3″ values between the 2 animals. It was determined that 30 min of scanning data were sufficient to derive V3″ values using kinetic, graphical (arterial input and reference-region input), and SRTM analyses. Conclusion: This study indicates that 11C-NPA is a suitable PET tracer to quantify the agonist high-affinity sites of D2-like receptors.

AB - (-)-N-11C-propyl-norapomorphine (11C-NPA) is a new dopamine agonist PET radiotracer that holds potential for imaging the high-affinity states of dopamine D2-like receptors in the living brain. The goal of this study was to develop and evaluate analytic strategies to derive in vivo 11C-NPA binding parameters. Methods: Two baboons were scanned 4 times after 11C-NPA injections. The metabolite-corrected arterial input functions were measured. Regional brain time-activity curves were analyzed with kinetic and graphical analyses, using the arterial time-activity curve as the input function. Data were also analyzed with the simplified reference-tissue model (SRTM) and graphical analysis with reference-region input. Results: 11C-NPA exhibited moderately fast metabolism, with 31% ± 5% of arterial plasma concentration corresponding to the parent compound at 40 min after injection. Plasma clearance was 29 ± 1 L/h, and plasma free fraction (f1) was 5% ± 1%. For kinetic analysis, a 1-tissue compartment model (1TCM) provided a good fit to the data and more robust derivations of the tissue distribution volumes (VT, in mL/g) than a 2-tissue compartment model (2TCM). Using 1TCM, VTs in the cerebellum and striatum were 3.4 ± 0.4 and 7.5 ± 2 mL/g, respectively, which led to estimates of striatal binding potential (BP) of 4.0 ± 1.1 mL/g and striatal equilibrium specific-to-nonspecific partition coefficient (V3″) of 1.2 ± 0.2. VT values derived with graphical analysis were well correlated with but slightly lower than VT values derived with kinetic analysis. V3″ values derived with SRTM were well correlated with but slightly higher than V3″ values derived with kinetic analysis. Using any method, a significant difference was detected in BP and V3″ values between the 2 animals. It was determined that 30 min of scanning data were sufficient to derive V3″ values using kinetic, graphical (arterial input and reference-region input), and SRTM analyses. Conclusion: This study indicates that 11C-NPA is a suitable PET tracer to quantify the agonist high-affinity sites of D2-like receptors.

KW - C-NPA

KW - D agonist

KW - Dopamine

KW - Nonhuman primate

KW - PET

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VL - 45

SP - 338

EP - 346

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

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Hwang DR, Narendran R, Huang Y, Slifstein M, Talbot PS, Sudo Y et al. Quantitative analysis of (-)-N-11C-propyl-norapomorphine in vivo binding in nonhuman primates. Journal of Nuclear Medicine. 2004 Feb 1;45(2):338-346.