Reproducibility of PET measurement for presynaptic dopaminergic functions using L-[β-(11)C]DOPA and [(18)F]FE-PE2I in humans.
OBJECTIVE
Recent PET studies have indicated altered presynaptic function and relation with psychotic symptoms in patients with schizophrenia. The L-[β-(11)C]DOPA uptake rate reflects the dopamine synthesis capacity (kref), whereas the nondisplaceable binding potential (BPND) of [(18)F]FE-PE2I reflects the dopamine transporter availability. Although the kref values of L-[β-(11)C]DOPA and the BPND of [(18)F]FE-PE2I can be potential markers for evaluating the severity of positive symptoms, test-retest reproducibility has not been confirmed. The purpose of this study was to investigate the test-retest reproducibility of kref values of L-[β-(11)C]DOPA and that of BPND of [(18)F]FE-PE2I in the striatum and midbrain in healthy humans.


METHODS
Twelve healthy male volunteers underwent two PET studies on separate days. Each PET study comprised two PET scans, one with L-[β-(11)C]DOPA and the other with [(18)F]FE-PE2I. Volumes of interest were defined for the caudate, putamen, midbrain, and thalamus. Test-retest reproducibility was assessed in terms of intrasubject variability (absolute variability) and reliability [intraclass correlation coefficient (ICC)].


RESULTS
The absolute variability values of kref and BPND were 4.8-25.7% on average for the caudate, putamen, midbrain, and thalamus. The ICC values of the kref values of L-[β-(11)C]DOPA were 0.78, 0.71, 0.77, and 0.77 for the caudate, putamen, midbrain, and thalamus, respectively. The ICC values of the BPND of [(18)F]FE-PE2I were 0.83, 0.88, 0.71, and 0.70 for the caudate, putamen, midbrain, and thalamus, respectively.


CONCLUSIONS
We found good test-retest reproducibility for the kref values of L-[β-(11)C]DOPA and that for the BPND of [(18)F]FE-PE2I in the striatum and midbrain, indicating the reliability of clinical investigation using PET with L-[β-(11)C]DOPA and [(18)F]FE-PE2I.
aMolecular Neuroimaging Program bBiophysics Program cMolecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba dDepartment of Neuropsychiatry, Nippon Medical School, Tokyo, Japan eDepartment of Clinical Neuroscience, Karolinska Institutet, Psychiatry Section, Stockholm, Sweden.
Masayuki
M
Suzuki
Hiroshi
H
Ito
Fumitoshi
F
Kodaka
Harumasa
H
Takano
Yasuyuki
Y
Kimura
Hironobu
H
Fujiwara
Takeshi
T
Sasaki
Keisuke
K
Takahata
Tsuyoshi
T
Nogami
Tomohisa
T
Nagashima
Nobuki
N
Nengaki
Kazunori
K
Kawamura
Ming-Rong
MR
Zhang
Andrea
A
Varrone
Christer
C
Halldin
Yoshiro
Y
Okubo
Tetsuya
T
Suhara
D000328:Adult; D002250:Carbon Radioisotopes; D004295:Dihydroxyphenylalanine; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000000981:diagnostic imaging / Q000378:metabolism; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism; D009662:Nortropanes; D049268:Positron-Emission Tomography / Q000379:methods*; D015203:Reproducibility of Results; D013569:Synapses; D055815:Young Adult
C543996:(E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta-(4'-methyl-phenyl) nortropane; D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D009662:Nortropanes; D004295:Dihydroxyphenylalanine; D004298:Dopamine