The role of radiotracer imaging in Parkinson disease

B. Ravina, D. Eidelberg, J. E. Ahlskog, R. L. Albin, D. J. Brooks, M. Carbon, V. Dhawan, A. Feigin, S. Fahn, M. Guttman, K. Gwinn-Hardy, H. McFarland, R. Innis, R. G. Katz, K. Kieburtz, S. J. Kish, N. Lange, J. W. Langston, K. Marek, L. Morin & 12 others C. Moy, D. Murphy, W. H. Oertel, G. Oliver, Y. Palesch, W. Powers, J. Seibyl, Kapil Dev Sethi, C. W. Shults, P. Sheehy, A. J. Stoessl, R. Holloway

Research output: Contribution to journalReview article

274 Citations (Scopus)

Abstract

Radiotracer imaging (RTI) of the nigrostriatal dopaminergic system is a widely used but controversial biomarker in Parkinson disease (PD). Here the authors review the concepts of biomarker development and the evidence to support the use of four radiotracers as biomarkers in PD: [18F]fluorodopa PET, (+)-[11C]dihydrotetrabenazine PET, [123I] β-CIT SPECT, and [18F] fluorodeoxyglucose PET. Biomarkers used to study disease biology and facilitate drug discovery and early human trials rely on evidence that they are measuring relevant biologic processes. The four tracers fulfill this criterion, although they do not measure the number or density of dopaminergic neurons. Biomarkers used as diagnostic tests, prognostic tools, or surrogate endpoints must not only have biologic relevance but also a strong linkage to the clinical outcome of interest. No radiotracers fulfill these criteria, and current evidence does not support the use of imaging as a diagnostic tool in clinical practice or as a surrogate endpoint in clinical trials. Mechanistic information added by RTI to clinical trials may be difficult to interpret because of uncertainty about the interaction between the interventions and the tracer.

Original languageEnglish (US)
Pages (from-to)208-215
Number of pages8
JournalNeurology
Volume64
Issue number2
DOIs
StatePublished - Jan 25 2005

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Parkinson Disease
Biomarkers
Clinical Trials
Dopaminergic Neurons
Fluorodeoxyglucose F18
Drug Discovery
Single-Photon Emission-Computed Tomography
Routine Diagnostic Tests
Uncertainty

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Ravina, B., Eidelberg, D., Ahlskog, J. E., Albin, R. L., Brooks, D. J., Carbon, M., ... Holloway, R. (2005). The role of radiotracer imaging in Parkinson disease. Neurology, 64(2), 208-215. https://doi.org/10.1212/01.WNL.0000149403.14458.7F

The role of radiotracer imaging in Parkinson disease. / Ravina, B.; Eidelberg, D.; Ahlskog, J. E.; Albin, R. L.; Brooks, D. J.; Carbon, M.; Dhawan, V.; Feigin, A.; Fahn, S.; Guttman, M.; Gwinn-Hardy, K.; McFarland, H.; Innis, R.; Katz, R. G.; Kieburtz, K.; Kish, S. J.; Lange, N.; Langston, J. W.; Marek, K.; Morin, L.; Moy, C.; Murphy, D.; Oertel, W. H.; Oliver, G.; Palesch, Y.; Powers, W.; Seibyl, J.; Sethi, Kapil Dev; Shults, C. W.; Sheehy, P.; Stoessl, A. J.; Holloway, R.

In: Neurology, Vol. 64, No. 2, 25.01.2005, p. 208-215.

Research output: Contribution to journalReview article

Ravina, B, Eidelberg, D, Ahlskog, JE, Albin, RL, Brooks, DJ, Carbon, M, Dhawan, V, Feigin, A, Fahn, S, Guttman, M, Gwinn-Hardy, K, McFarland, H, Innis, R, Katz, RG, Kieburtz, K, Kish, SJ, Lange, N, Langston, JW, Marek, K, Morin, L, Moy, C, Murphy, D, Oertel, WH, Oliver, G, Palesch, Y, Powers, W, Seibyl, J, Sethi, KD, Shults, CW, Sheehy, P, Stoessl, AJ & Holloway, R 2005, 'The role of radiotracer imaging in Parkinson disease', Neurology, vol. 64, no. 2, pp. 208-215. https://doi.org/10.1212/01.WNL.0000149403.14458.7F
Ravina B, Eidelberg D, Ahlskog JE, Albin RL, Brooks DJ, Carbon M et al. The role of radiotracer imaging in Parkinson disease. Neurology. 2005 Jan 25;64(2):208-215. https://doi.org/10.1212/01.WNL.0000149403.14458.7F
Ravina, B. ; Eidelberg, D. ; Ahlskog, J. E. ; Albin, R. L. ; Brooks, D. J. ; Carbon, M. ; Dhawan, V. ; Feigin, A. ; Fahn, S. ; Guttman, M. ; Gwinn-Hardy, K. ; McFarland, H. ; Innis, R. ; Katz, R. G. ; Kieburtz, K. ; Kish, S. J. ; Lange, N. ; Langston, J. W. ; Marek, K. ; Morin, L. ; Moy, C. ; Murphy, D. ; Oertel, W. H. ; Oliver, G. ; Palesch, Y. ; Powers, W. ; Seibyl, J. ; Sethi, Kapil Dev ; Shults, C. W. ; Sheehy, P. ; Stoessl, A. J. ; Holloway, R. / The role of radiotracer imaging in Parkinson disease. In: Neurology. 2005 ; Vol. 64, No. 2. pp. 208-215.
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AU - Brooks, D. J.

AU - Carbon, M.

AU - Dhawan, V.

AU - Feigin, A.

AU - Fahn, S.

AU - Guttman, M.

AU - Gwinn-Hardy, K.

AU - McFarland, H.

AU - Innis, R.

AU - Katz, R. G.

AU - Kieburtz, K.

AU - Kish, S. J.

AU - Lange, N.

AU - Langston, J. W.

AU - Marek, K.

AU - Morin, L.

AU - Moy, C.

AU - Murphy, D.

AU - Oertel, W. H.

AU - Oliver, G.

AU - Palesch, Y.

AU - Powers, W.

AU - Seibyl, J.

AU - Sethi, Kapil Dev

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N2 - Radiotracer imaging (RTI) of the nigrostriatal dopaminergic system is a widely used but controversial biomarker in Parkinson disease (PD). Here the authors review the concepts of biomarker development and the evidence to support the use of four radiotracers as biomarkers in PD: [18F]fluorodopa PET, (+)-[11C]dihydrotetrabenazine PET, [123I] β-CIT SPECT, and [18F] fluorodeoxyglucose PET. Biomarkers used to study disease biology and facilitate drug discovery and early human trials rely on evidence that they are measuring relevant biologic processes. The four tracers fulfill this criterion, although they do not measure the number or density of dopaminergic neurons. Biomarkers used as diagnostic tests, prognostic tools, or surrogate endpoints must not only have biologic relevance but also a strong linkage to the clinical outcome of interest. No radiotracers fulfill these criteria, and current evidence does not support the use of imaging as a diagnostic tool in clinical practice or as a surrogate endpoint in clinical trials. Mechanistic information added by RTI to clinical trials may be difficult to interpret because of uncertainty about the interaction between the interventions and the tracer.

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