The role of radiotracer imaging in Parkinson disease
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,...
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| Veröffentlicht in: | Neurology 2005-01, Vol.64 (2), p.208-215 |
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| creator | RAVINA, B EIDELBERG, D GWINN-HARDY, K MCFARLAND, H INNIS, R KATZ, R. G KIEBURTZ, K KISH, S. J LANGE, N LANGSTON, J. W MAREK, K MORIN, L AHLSKOG, J. E MOY, C MURPHY, D OERTEL, W. H OLIVER, G PALESCH, Y POWERS, W SEIBYL, J SETHI, K. D SHULTS, C. W SHEEHY, P ALBIN, R. L STOESSL, A. J HOLLOWAY, R BROOKS, D. J CARBON, M DHAWAN, V FEIGIN, A FAHN, S GUTTMAN, M |
| description | 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]beta-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. |
| doi_str_mv | 10.1212/01.wnl.0000149403.14458.7f |
| format | Article |
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G ; KIEBURTZ, K ; KISH, S. J ; LANGE, N ; LANGSTON, J. W ; MAREK, K ; MORIN, L ; AHLSKOG, J. E ; MOY, C ; MURPHY, D ; OERTEL, W. H ; OLIVER, G ; PALESCH, Y ; POWERS, W ; SEIBYL, J ; SETHI, K. D ; SHULTS, C. W ; SHEEHY, P ; ALBIN, R. L ; STOESSL, A. J ; HOLLOWAY, R ; BROOKS, D. J ; CARBON, M ; DHAWAN, V ; FEIGIN, A ; FAHN, S ; GUTTMAN, M</creator><creatorcontrib>RAVINA, B ; EIDELBERG, D ; GWINN-HARDY, K ; MCFARLAND, H ; INNIS, R ; KATZ, R. G ; KIEBURTZ, K ; KISH, S. J ; LANGE, N ; LANGSTON, J. W ; MAREK, K ; MORIN, L ; AHLSKOG, J. E ; MOY, C ; MURPHY, D ; OERTEL, W. H ; OLIVER, G ; PALESCH, Y ; POWERS, W ; SEIBYL, J ; SETHI, K. D ; SHULTS, C. W ; SHEEHY, P ; ALBIN, R. L ; STOESSL, A. J ; HOLLOWAY, R ; BROOKS, D. J ; CARBON, M ; DHAWAN, V ; FEIGIN, A ; FAHN, S ; GUTTMAN, M</creatorcontrib><description>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]beta-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.</description><identifier>ISSN: 0028-3878</identifier><identifier>EISSN: 1526-632X</identifier><identifier>DOI: 10.1212/01.wnl.0000149403.14458.7f</identifier><identifier>PMID: 15668415</identifier><identifier>CODEN: NEURAI</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Biological and medical sciences ; Biomarkers ; Biotransformation ; Blood-Brain Barrier ; Carbon Radioisotopes - pharmacokinetics ; Clinical Trials as Topic - methods ; Cocaine - analogs & derivatives ; Cocaine - pharmacokinetics ; Corpus Striatum - diagnostic imaging ; Corpus Striatum - metabolism ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Dihydroxyphenylalanine - analogs & derivatives ; Dihydroxyphenylalanine - pharmacokinetics ; Dopamine - metabolism ; Fluorine Radioisotopes - pharmacokinetics ; Fluorodeoxyglucose F18 - pharmacokinetics ; Forecasting ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; Iodine Radioisotopes - pharmacokinetics ; Medical sciences ; Nervous system ; Neurology ; Neurons - chemistry ; Neurons - diagnostic imaging ; Parkinson Disease - diagnosis ; Parkinson Disease - diagnostic imaging ; Parkinson Disease - therapy ; Positron-Emission Tomography ; Prognosis ; Radiodiagnosis. Nmr imagery. Nmr spectrometry ; Radiopharmaceuticals - pharmacokinetics ; Receptors, Dopamine - metabolism ; Substantia Nigra - diagnostic imaging ; Substantia Nigra - metabolism ; Tetrabenazine - analogs & derivatives ; Tetrabenazine - pharmacokinetics ; Tomography, Emission-Computed, Single-Photon</subject><ispartof>Neurology, 2005-01, Vol.64 (2), p.208-215</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-9274a451d8091ca9a10f7e8a98511a838b5c72587341708856235643db93345b3</citedby><cites>FETCH-LOGICAL-c413t-9274a451d8091ca9a10f7e8a98511a838b5c72587341708856235643db93345b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16647956$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15668415$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>RAVINA, B</creatorcontrib><creatorcontrib>EIDELBERG, D</creatorcontrib><creatorcontrib>GWINN-HARDY, K</creatorcontrib><creatorcontrib>MCFARLAND, H</creatorcontrib><creatorcontrib>INNIS, R</creatorcontrib><creatorcontrib>KATZ, R. G</creatorcontrib><creatorcontrib>KIEBURTZ, K</creatorcontrib><creatorcontrib>KISH, S. J</creatorcontrib><creatorcontrib>LANGE, N</creatorcontrib><creatorcontrib>LANGSTON, J. W</creatorcontrib><creatorcontrib>MAREK, K</creatorcontrib><creatorcontrib>MORIN, L</creatorcontrib><creatorcontrib>AHLSKOG, J. E</creatorcontrib><creatorcontrib>MOY, C</creatorcontrib><creatorcontrib>MURPHY, D</creatorcontrib><creatorcontrib>OERTEL, W. H</creatorcontrib><creatorcontrib>OLIVER, G</creatorcontrib><creatorcontrib>PALESCH, Y</creatorcontrib><creatorcontrib>POWERS, W</creatorcontrib><creatorcontrib>SEIBYL, J</creatorcontrib><creatorcontrib>SETHI, K. D</creatorcontrib><creatorcontrib>SHULTS, C. W</creatorcontrib><creatorcontrib>SHEEHY, P</creatorcontrib><creatorcontrib>ALBIN, R. L</creatorcontrib><creatorcontrib>STOESSL, A. J</creatorcontrib><creatorcontrib>HOLLOWAY, R</creatorcontrib><creatorcontrib>BROOKS, D. J</creatorcontrib><creatorcontrib>CARBON, M</creatorcontrib><creatorcontrib>DHAWAN, V</creatorcontrib><creatorcontrib>FEIGIN, A</creatorcontrib><creatorcontrib>FAHN, S</creatorcontrib><creatorcontrib>GUTTMAN, M</creatorcontrib><title>The role of radiotracer imaging in Parkinson disease</title><title>Neurology</title><addtitle>Neurology</addtitle><description>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]beta-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.</description><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Biotransformation</subject><subject>Blood-Brain Barrier</subject><subject>Carbon Radioisotopes - pharmacokinetics</subject><subject>Clinical Trials as Topic - methods</subject><subject>Cocaine - analogs & derivatives</subject><subject>Cocaine - pharmacokinetics</subject><subject>Corpus Striatum - diagnostic imaging</subject><subject>Corpus Striatum - metabolism</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Dihydroxyphenylalanine - analogs & derivatives</subject><subject>Dihydroxyphenylalanine - pharmacokinetics</subject><subject>Dopamine - metabolism</subject><subject>Fluorine Radioisotopes - pharmacokinetics</subject><subject>Fluorodeoxyglucose F18 - pharmacokinetics</subject><subject>Forecasting</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Iodine Radioisotopes - pharmacokinetics</subject><subject>Medical sciences</subject><subject>Nervous system</subject><subject>Neurology</subject><subject>Neurons - chemistry</subject><subject>Neurons - diagnostic imaging</subject><subject>Parkinson Disease - diagnosis</subject><subject>Parkinson Disease - diagnostic imaging</subject><subject>Parkinson Disease - therapy</subject><subject>Positron-Emission Tomography</subject><subject>Prognosis</subject><subject>Radiodiagnosis. Nmr imagery. Nmr spectrometry</subject><subject>Radiopharmaceuticals - pharmacokinetics</subject><subject>Receptors, Dopamine - metabolism</subject><subject>Substantia Nigra - diagnostic imaging</subject><subject>Substantia Nigra - metabolism</subject><subject>Tetrabenazine - analogs & derivatives</subject><subject>Tetrabenazine - pharmacokinetics</subject><subject>Tomography, Emission-Computed, Single-Photon</subject><issn>0028-3878</issn><issn>1526-632X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1Lw0AQhhdRbK3-BQmC3hJ39nu9SbEqFPVQ0duy2Wzqaprobov474020LnM5XnfYR6EzgAXQIBcYii-26bA_QDTDNMCGOOqkPUeGgMnIheUvO6jMcZE5VRJNUJHKb33OCdSH6IRcCEUAz5GbPHms9g1PuvqLNoqdOtonY9ZWNllaJdZaLMnGz9Cm7o2q0LyNvljdFDbJvmTYU_Q8-xmMb3L54-399Pree4Y0HWuiWSWcagU1uCstoBr6ZXVigNYRVXJnSRcScpAYqW4IJQLRqtSU8p4SSfoYtv7GbuvjU9rswrJ-aaxre82yQhJFaGE9ODVFnSxSyn62nzG_oH4YwCbP2cGg3l5mJudM_PvzMhZHz4drmzKla920UFSD5wPgE3ONnW0rQtpxwnBpOaC_gJ2MXLA</recordid><startdate>20050125</startdate><enddate>20050125</enddate><creator>RAVINA, B</creator><creator>EIDELBERG, D</creator><creator>GWINN-HARDY, K</creator><creator>MCFARLAND, H</creator><creator>INNIS, R</creator><creator>KATZ, R. 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J ; CARBON, M ; DHAWAN, V ; FEIGIN, A ; FAHN, S ; GUTTMAN, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-9274a451d8091ca9a10f7e8a98511a838b5c72587341708856235643db93345b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Biotransformation</topic><topic>Blood-Brain Barrier</topic><topic>Carbon Radioisotopes - pharmacokinetics</topic><topic>Clinical Trials as Topic - methods</topic><topic>Cocaine - analogs & derivatives</topic><topic>Cocaine - pharmacokinetics</topic><topic>Corpus Striatum - diagnostic imaging</topic><topic>Corpus Striatum - metabolism</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Dihydroxyphenylalanine - analogs & derivatives</topic><topic>Dihydroxyphenylalanine - pharmacokinetics</topic><topic>Dopamine - metabolism</topic><topic>Fluorine Radioisotopes - pharmacokinetics</topic><topic>Fluorodeoxyglucose F18 - pharmacokinetics</topic><topic>Forecasting</topic><topic>Humans</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Iodine Radioisotopes - pharmacokinetics</topic><topic>Medical sciences</topic><topic>Nervous system</topic><topic>Neurology</topic><topic>Neurons - chemistry</topic><topic>Neurons - diagnostic imaging</topic><topic>Parkinson Disease - diagnosis</topic><topic>Parkinson Disease - diagnostic imaging</topic><topic>Parkinson Disease - therapy</topic><topic>Positron-Emission Tomography</topic><topic>Prognosis</topic><topic>Radiodiagnosis. Nmr imagery. Nmr spectrometry</topic><topic>Radiopharmaceuticals - pharmacokinetics</topic><topic>Receptors, Dopamine - metabolism</topic><topic>Substantia Nigra - diagnostic imaging</topic><topic>Substantia Nigra - metabolism</topic><topic>Tetrabenazine - analogs & derivatives</topic><topic>Tetrabenazine - pharmacokinetics</topic><topic>Tomography, Emission-Computed, Single-Photon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>RAVINA, B</creatorcontrib><creatorcontrib>EIDELBERG, D</creatorcontrib><creatorcontrib>GWINN-HARDY, K</creatorcontrib><creatorcontrib>MCFARLAND, H</creatorcontrib><creatorcontrib>INNIS, R</creatorcontrib><creatorcontrib>KATZ, R. G</creatorcontrib><creatorcontrib>KIEBURTZ, K</creatorcontrib><creatorcontrib>KISH, S. J</creatorcontrib><creatorcontrib>LANGE, N</creatorcontrib><creatorcontrib>LANGSTON, J. W</creatorcontrib><creatorcontrib>MAREK, K</creatorcontrib><creatorcontrib>MORIN, L</creatorcontrib><creatorcontrib>AHLSKOG, J. 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J</creatorcontrib><creatorcontrib>CARBON, M</creatorcontrib><creatorcontrib>DHAWAN, V</creatorcontrib><creatorcontrib>FEIGIN, A</creatorcontrib><creatorcontrib>FAHN, S</creatorcontrib><creatorcontrib>GUTTMAN, M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>RAVINA, B</au><au>EIDELBERG, D</au><au>GWINN-HARDY, K</au><au>MCFARLAND, H</au><au>INNIS, R</au><au>KATZ, R. G</au><au>KIEBURTZ, K</au><au>KISH, S. J</au><au>LANGE, N</au><au>LANGSTON, J. W</au><au>MAREK, K</au><au>MORIN, L</au><au>AHLSKOG, J. E</au><au>MOY, C</au><au>MURPHY, D</au><au>OERTEL, W. 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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]beta-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.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>15668415</pmid><doi>10.1212/01.wnl.0000149403.14458.7f</doi><tpages>8</tpages></addata></record> |
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| ispartof | Neurology, 2005-01, Vol.64 (2), p.208-215 |
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| source | MEDLINE; Alma/SFX Local Collection; Journals@Ovid Complete |
| subjects | Biological and medical sciences Biomarkers Biotransformation Blood-Brain Barrier Carbon Radioisotopes - pharmacokinetics Clinical Trials as Topic - methods Cocaine - analogs & derivatives Cocaine - pharmacokinetics Corpus Striatum - diagnostic imaging Corpus Striatum - metabolism Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Dihydroxyphenylalanine - analogs & derivatives Dihydroxyphenylalanine - pharmacokinetics Dopamine - metabolism Fluorine Radioisotopes - pharmacokinetics Fluorodeoxyglucose F18 - pharmacokinetics Forecasting Humans Investigative techniques, diagnostic techniques (general aspects) Iodine Radioisotopes - pharmacokinetics Medical sciences Nervous system Neurology Neurons - chemistry Neurons - diagnostic imaging Parkinson Disease - diagnosis Parkinson Disease - diagnostic imaging Parkinson Disease - therapy Positron-Emission Tomography Prognosis Radiodiagnosis. Nmr imagery. Nmr spectrometry Radiopharmaceuticals - pharmacokinetics Receptors, Dopamine - metabolism Substantia Nigra - diagnostic imaging Substantia Nigra - metabolism Tetrabenazine - analogs & derivatives Tetrabenazine - pharmacokinetics Tomography, Emission-Computed, Single-Photon |
| title | The role of radiotracer imaging in Parkinson disease |
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