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, (+)-[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.
Ravina
B
B
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. ravinab@ninds.nih.gov
Eidelberg
D
D
Ahlskog
J E
JE
Albin
R L
RL
Brooks
D J
DJ
Carbon
M
M
Dhawan
V
V
Feigin
A
A
Fahn
S
S
Guttman
M
M
Gwinn-Hardy
K
K
McFarland
H
H
Innis
R
R
Katz
R G
RG
Kieburtz
K
K
Kish
S J
SJ
Lange
N
N
Langston
J W
JW
Marek
K
K
Morin
L
L
Moy
C
C
Murphy
D
D
Oertel
W H
WH
Oliver
G
G
Palesch
Y
Y
Powers
W
W
Seibyl
J
J
Sethi
K D
KD
Shults
C W
CW
Sheehy
P
P
Stoessl
A J
AJ
Holloway
R
R
D015415:Biomarkers; D001711:Biotransformation; D001812:Blood-Brain Barrier; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002986:Clinical Trials as Topic / Q000379:methods; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004298:Dopamine / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005544:Forecasting; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D009474:Neurons / Q000737:chemistry / Q000000981:diagnostic imaging; D010300:Parkinson Disease / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000628:therapy; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011954:Receptors, Dopamine / Q000378:metabolism; D013378:Substantia Nigra / Q000000981:diagnostic imaging* / Q000378:metabolism; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon
D015415:Biomarkers; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011954:Receptors, Dopamine; D019788:Fluorodeoxyglucose F18; C043437:fluorodopa F 18; C032811:dihydrotetrabenazine; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D004295:Dihydroxyphenylalanine; D003042:Cocaine; D004298:Dopamine; D013747:Tetrabenazine