Biodistribution, Radiation Dosimetry, and Kinetic Modeling of [18F]FPEB PET Imaging of mGluR5 in Healthy Asian Subjects.

Background

Metabotropic glutamate receptor subtype 5 (mGluR5) is a promising therapeutic target for a range of neuropsychiatric disorders, and [18F]FPEB is a PET radioligand developed for imaging central mGluR5 receptor availability. This study aimed to determine the biodistribution, kinetic characteristics, and radiation dosimetry of [18F]FPEB in healthy Asian subjects and to evaluate the feasibility of reference tissue models as alternatives to conventional blood-based kinetic modeling.

Methods

Five healthy Asian male volunteers underwent whole-body and dynamic brain PET imaging following administration of [18F]FPEB. Radiation dosimetry was estimated using OLINDA/EXM software. Tracer kinetics were analyzed using both blood-based compartmental models and reference tissue models to derive regional binding potentials (BPND) and volumes of distribution. Model performance was assessed using the Akaike Information Criterion (AIC).

Results

The mean whole-body effective radiation dose was 0.703 mSv/mCi, with the gallbladder identified as the critical organ receiving the highest absorbed dose (5.63 mGy/mCi). Brain time-activity curves demonstrated the highest tracer uptake in the nucleus accumbens, followed by the cingulate gyrus, putamen, and insula, with moderate uptake in the thalamus and globus pallidus and the lowest uptake in the brainstem and cerebellum. Using the simplified reference tissue models (SRTM/SRTM2), the highest BPND values were observed in the nucleus accumbens, followed by the cingulate gyrus, putamen, and insula. In contrast, two-tissue compartment models (2TCM/2TCM-C) showed the highest BPND values in the hippocampus, followed by the amygdala, nucleus accumbens, and caudate nucleus. Although differences were observed in the absolute BPND values and regional ranking, both modeling approaches identified similar brain regions with high mGluR5 binding.

Conclusions

[18F]FPEB demonstrated a favorable radiation dosimetry profile and supports the feasibility of reference tissue models for BPND estimation in healthy Asian subjects. These findings provide preliminary baseline data, although validation in larger cohorts is needed to confirm the pharmacokinetic characteristics and modeling approach.