Pet imaging a MPTP-induced mouse model of Parkinson's disease using the fluoropropyl-dihydrotetrabenazine analog [18F]-DTBZ (AV-133)

James S. Toomey, Shilpa Bhatia, La'Wanda T. Moon, Elysse A. Orchard, Kerrie H. Tainter, Stephen J. Lokitz, Tracee Terry, James Michael Mathis, Andrew D. Penman

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Abstract

Parkinson's disease (PD) is characterized by the loss of dopamine-producing neurons in the nigrostriatal system. Numerous researchers in the past have attempted to track the progression of dopaminergic depletion in PD. We applied a quantitative non-invasive PET imaging technique to follow this degeneration process in an MPTP-induced mouse model of PD. The VMAT2 ligand 18F-DTBZ (AV-133) was used as a radioactive tracer in our imaging experiments to monitor the changes of the dopaminergic system. Intraperitoneal administrations of MPTP (a neurotoxin) were delivered to mice at regular intervals to induce lesions consistent with PD. Our results indicate a significant decline in the levels of striatal dopamine and its metabolites (DOPAC and HVA) following MPTP treatment as determined by HPLC method. Images obtained by positron emission tomography revealed uptake of 18F-DTBZ analog in the mouse striatum. However, reduction in radioligand binding was evident in the striatum of MPTP lesioned animals as compared with the control group. Immunohistochemical analysis further confirmed PET imaging results and indicated the progressive loss of dopaminergic neurons in treated animals compared with the control counterparts. In conclusion, our findings suggest that MPTP induced PD in mouse model is appropriate to follow the degeneration of dopaminergic system and that 18F-DTBZ analog is a potentially sensitive radiotracer that can used to diagnose changes associated with PD by PET imaging modality.

Original languageEnglish
Article numbere39041
JournalPLoS ONE
Volume7
Issue number6
DOIs
StatePublished - 18 Jun 2012

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Parkinson disease
Pets
pets
Parkinson Disease
positron-emission tomography
animal models
image analysis
Imaging techniques
Dopaminergic Neurons
dopamine
Neurons
Dopamine
Animals
neurons
Radioactive Tracers
Corpus Striatum
3,4-Dihydroxyphenylacetic Acid
radiolabeling
Positron emission tomography

Cite this

Toomey, J. S., Bhatia, S., Moon, LW. T., Orchard, E. A., Tainter, K. H., Lokitz, S. J., ... Penman, A. D. (2012). Pet imaging a MPTP-induced mouse model of Parkinson's disease using the fluoropropyl-dihydrotetrabenazine analog [18F]-DTBZ (AV-133). PLoS ONE, 7(6), [e39041]. https://doi.org/10.1371/journal.pone.0039041
Toomey, James S. ; Bhatia, Shilpa ; Moon, La'Wanda T. ; Orchard, Elysse A. ; Tainter, Kerrie H. ; Lokitz, Stephen J. ; Terry, Tracee ; Mathis, James Michael ; Penman, Andrew D. / Pet imaging a MPTP-induced mouse model of Parkinson's disease using the fluoropropyl-dihydrotetrabenazine analog [18F]-DTBZ (AV-133). In: PLoS ONE. 2012 ; Vol. 7, No. 6.
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abstract = "Parkinson's disease (PD) is characterized by the loss of dopamine-producing neurons in the nigrostriatal system. Numerous researchers in the past have attempted to track the progression of dopaminergic depletion in PD. We applied a quantitative non-invasive PET imaging technique to follow this degeneration process in an MPTP-induced mouse model of PD. The VMAT2 ligand 18F-DTBZ (AV-133) was used as a radioactive tracer in our imaging experiments to monitor the changes of the dopaminergic system. Intraperitoneal administrations of MPTP (a neurotoxin) were delivered to mice at regular intervals to induce lesions consistent with PD. Our results indicate a significant decline in the levels of striatal dopamine and its metabolites (DOPAC and HVA) following MPTP treatment as determined by HPLC method. Images obtained by positron emission tomography revealed uptake of 18F-DTBZ analog in the mouse striatum. However, reduction in radioligand binding was evident in the striatum of MPTP lesioned animals as compared with the control group. Immunohistochemical analysis further confirmed PET imaging results and indicated the progressive loss of dopaminergic neurons in treated animals compared with the control counterparts. In conclusion, our findings suggest that MPTP induced PD in mouse model is appropriate to follow the degeneration of dopaminergic system and that 18F-DTBZ analog is a potentially sensitive radiotracer that can used to diagnose changes associated with PD by PET imaging modality.",
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Pet imaging a MPTP-induced mouse model of Parkinson's disease using the fluoropropyl-dihydrotetrabenazine analog [18F]-DTBZ (AV-133). / Toomey, James S.; Bhatia, Shilpa; Moon, La'Wanda T.; Orchard, Elysse A.; Tainter, Kerrie H.; Lokitz, Stephen J.; Terry, Tracee; Mathis, James Michael; Penman, Andrew D.

In: PLoS ONE, Vol. 7, No. 6, e39041, 18.06.2012.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Pet imaging a MPTP-induced mouse model of Parkinson's disease using the fluoropropyl-dihydrotetrabenazine analog [18F]-DTBZ (AV-133)

AU - Toomey, James S.

AU - Bhatia, Shilpa

AU - Moon, La'Wanda T.

AU - Orchard, Elysse A.

AU - Tainter, Kerrie H.

AU - Lokitz, Stephen J.

AU - Terry, Tracee

AU - Mathis, James Michael

AU - Penman, Andrew D.

PY - 2012/6/18

Y1 - 2012/6/18

N2 - Parkinson's disease (PD) is characterized by the loss of dopamine-producing neurons in the nigrostriatal system. Numerous researchers in the past have attempted to track the progression of dopaminergic depletion in PD. We applied a quantitative non-invasive PET imaging technique to follow this degeneration process in an MPTP-induced mouse model of PD. The VMAT2 ligand 18F-DTBZ (AV-133) was used as a radioactive tracer in our imaging experiments to monitor the changes of the dopaminergic system. Intraperitoneal administrations of MPTP (a neurotoxin) were delivered to mice at regular intervals to induce lesions consistent with PD. Our results indicate a significant decline in the levels of striatal dopamine and its metabolites (DOPAC and HVA) following MPTP treatment as determined by HPLC method. Images obtained by positron emission tomography revealed uptake of 18F-DTBZ analog in the mouse striatum. However, reduction in radioligand binding was evident in the striatum of MPTP lesioned animals as compared with the control group. Immunohistochemical analysis further confirmed PET imaging results and indicated the progressive loss of dopaminergic neurons in treated animals compared with the control counterparts. In conclusion, our findings suggest that MPTP induced PD in mouse model is appropriate to follow the degeneration of dopaminergic system and that 18F-DTBZ analog is a potentially sensitive radiotracer that can used to diagnose changes associated with PD by PET imaging modality.

AB - Parkinson's disease (PD) is characterized by the loss of dopamine-producing neurons in the nigrostriatal system. Numerous researchers in the past have attempted to track the progression of dopaminergic depletion in PD. We applied a quantitative non-invasive PET imaging technique to follow this degeneration process in an MPTP-induced mouse model of PD. The VMAT2 ligand 18F-DTBZ (AV-133) was used as a radioactive tracer in our imaging experiments to monitor the changes of the dopaminergic system. Intraperitoneal administrations of MPTP (a neurotoxin) were delivered to mice at regular intervals to induce lesions consistent with PD. Our results indicate a significant decline in the levels of striatal dopamine and its metabolites (DOPAC and HVA) following MPTP treatment as determined by HPLC method. Images obtained by positron emission tomography revealed uptake of 18F-DTBZ analog in the mouse striatum. However, reduction in radioligand binding was evident in the striatum of MPTP lesioned animals as compared with the control group. Immunohistochemical analysis further confirmed PET imaging results and indicated the progressive loss of dopaminergic neurons in treated animals compared with the control counterparts. In conclusion, our findings suggest that MPTP induced PD in mouse model is appropriate to follow the degeneration of dopaminergic system and that 18F-DTBZ analog is a potentially sensitive radiotracer that can used to diagnose changes associated with PD by PET imaging modality.

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