Nuclear medicine and biology · 2025
Estimation of the binding potential of the PET ligand [18F]FEDAC to translocator protein 18 kDa (TSPO) in the brain of experimental stroke model rats.
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Yamasaki Tomoteru, Zhang Yiding, Mori Wakana, Kumata Katsushi, Wakizaka Hidekatsu, Arashi Daisuke, Kurihara Yusuke, Ogawa Masanao, Nengaki Nobuki, Fujinaga Masayuki, Zhang Ming-Rong
Аннотация
PURPOSE: Translocator protein 18 kDa (TSPO) is a biomarker for neuroinflammation, and [18F]FEDAC was developed as a clinically usable radioligand for its imaging. Here, quantitative PET analyses of [18F]FEDAC in the brain of transient middle cerebral artery occlusion (tMCAO) rats were conducted for the first time.
METHODS: Quantitative PET analysis was performed on rats subjected to tMCAO, with blood sampling also conducted as part of the study. To estimate the kinetic parameters of [18F]FEDAC, two-tissue compartment model (2TCM) and simplified reference tissue model (SRTM) analyses were conducted.
RESULTS: The input rate (K1) and distribution volume (VT) (a macroparameter consisting of the K1-k4 rate constants from 2TCM analysis) of [18F]FEDAC in the ipsilateral area of tMCAO rats were 0.38 ± 0.19 mL/cm3/min and 5.4 ± 2.7 mL/cm3, respectively, which are roughly twice as high as those in the contralateral area. These results strongly suggest that ipsilateral binding potential (BPND), a quantitative index derived from the VT ratio with respect to the reference region, depends not only on the binding of [18F]FEDAC to TSPO, but also on increases in the input rate from blood. Therefore, in SRTM analyses, we corrected apparent BPND using R1, an index for probe delivery. In validation studies, SRTM analysis with the corrected BPND (corBPND), using the cerebellum as a reference, showed a high correlation with direct BPND (k3/k4) in 2TCM analyses.
CONCLUSION: The acquisition of quantitative PET images of TSPO distribution in the tMCAO rat brain was successfully achieved by scaling with corBPND.
METHODS: Quantitative PET analysis was performed on rats subjected to tMCAO, with blood sampling also conducted as part of the study. To estimate the kinetic parameters of [18F]FEDAC, two-tissue compartment model (2TCM) and simplified reference tissue model (SRTM) analyses were conducted.
RESULTS: The input rate (K1) and distribution volume (VT) (a macroparameter consisting of the K1-k4 rate constants from 2TCM analysis) of [18F]FEDAC in the ipsilateral area of tMCAO rats were 0.38 ± 0.19 mL/cm3/min and 5.4 ± 2.7 mL/cm3, respectively, which are roughly twice as high as those in the contralateral area. These results strongly suggest that ipsilateral binding potential (BPND), a quantitative index derived from the VT ratio with respect to the reference region, depends not only on the binding of [18F]FEDAC to TSPO, but also on increases in the input rate from blood. Therefore, in SRTM analyses, we corrected apparent BPND using R1, an index for probe delivery. In validation studies, SRTM analysis with the corrected BPND (corBPND), using the cerebellum as a reference, showed a high correlation with direct BPND (k3/k4) in 2TCM analyses.
CONCLUSION: The acquisition of quantitative PET images of TSPO distribution in the tMCAO rat brain was successfully achieved by scaling with corBPND.