[Phase 1 clinical study of 123I-IBF, a new radioligand for evaluating Dopamine D2 receptor with SPECT (II); pharmacokinetics study and quantification in the brain].
The pharmacokinetics of (S)-5-iodo-7-N-[(1-ethyl- 2-pyrrolidinyl)methyl]carboxamido-2,3-dihydro-benzofuran (123I-IBF) in the brain were studied in 12 healthy male volunteers as a Phase I clinical study. The striatum-to-frontal cortex count ratio (-1) (St/Fc-1), which is a semi-quantitative index of the binding potential of 123I-IBF reached 1.81 +/- 0.19 and 2.21 +/- 0.39 at 90-120 min and 180-210 min after intravenous injection of 123I-IBF. St/Fc-1 obtained by SPECT at these times correlated well with the distribution volume ratio (-1) (Vd(St)/Vd(Fc)-1) based on three-compartment model analysis using an input function obtained by intermittent arterial sampling. The binding potential (BPR), calculated by the curve-fitting method using the time-activity curve in the reference region, also correlated well with the Vd(St)/ Vd(Fc)-1. The intra-observer and inter-observer reproducibilities of the striatum-to-cerebral cortex count ratios obtained using fixed-shape regions of interest (template ROIs) were superior to those obtained using manual ROIs. These results suggest that 123I-IBF is a promising agent for non-invasive quantification of the dopamine D2 receptor (D2-R) binding potential by SPECT.
Yonekura
Y
Y
Biomedical Imaging Research Center, Fukui Medical University.
Sadato
N
N
Tsuchida
T
T
Uematsu
H
H
Nakamura
S
S
Onishi
Y
Y
Yamamoto
K
K
Ishii
Y
Y
D000328:Adult; D001572:Benzofurans / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D004341:Drug Evaluation; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D011874:Radiometry; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D001572:Benzofurans; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C062439:5-iodo-N-((1-ethyl-2-pyrrolidinyl)methyl)-2,3-dihydrobenzofurancarboxamide