# Characterization of in vivo binding kinetics and non-displaceable binding of [18F]SynvesT-1 in the rat brain

## TL;DR

This study examines how [18F]SynVesT-1 binds to the brain in rats, showing it works well but requires careful dosing to avoid errors.

## Contribution

The study provides new in vivo binding data for [18F]SynVesT-1 in rat brains and evaluates simplified quantification methods.

## Key findings

- Rapid brain uptake of [18F]SynVesT-1 was observed with dose-dependent reductions in radiotracer uptake.
- The two-tissue compartmental model best described the binding, with strong correlation between VT estimates and SUV30–60.
- A reference region was not found suitable, but SUV30–60 serves as a good surrogate for VT.

## Abstract

The synaptic vesicle glycoprotein 2 A (SV2A) has been identified as a biomarker of interest for neurological pathology. The SV2A specific radiotracer [18F]SynVesT-1 has shown good binding characteristics in mouse and human. The aim of this study was to characterize the binding parameters of [18F]SynVesT-1 in the rat brain and investigate simplified quantification methods. Twenty-one Positron Emission Tomography (PET) scans were conducted in male Sprague-Dawley rats with a bolus injection of [18F]SynVesT-1. Varying concentrations of non-radioactive SynVesT-1 were injected in an increasing mass dose paradigm (n = 21 ) with radioactivity in arterial blood recorded throughout. The radiometabolism was characterized in a further group (n = 7). The total volume of distribution (VT) was estimated using compartmental modelling and Logan plot and then compared to the standardized uptake value at 30–60 min (SUV30 − 60). Occupancy plots and a Lassen plot were generated.

The pharmacokinetics of [18F]SynVesT-1 PET showed rapid brain uptake and increasing doses of SynVesT-1 revealed a robust reduction in radiotracer uptake over all brain regions. The two-tissue compartmental model was most appropriate and the estimated VT was highly correlated with Logan VT, as was the SUV30 − 60. The VND was estimated to be 3.75, which is 12.5% (pons) to 22% (thalamus) of the VT. The estimated upper mass limit required to achieve 5% target occupancy is 0.48 µg/kg.

[18F]SynVesT-1 shows good characteristics for imaging the rat brain, however care must be taken to achieve adequate molar activity to avoid mass dose affects (< 5% occupancy). Data showed no suitable reference region for [18F]SynVesT-1, however SUV30 − 60 does give an appropriate surrogate for VT.

Not applicable.

The online version contains supplementary material available at 10.1186/s13550-025-01270-2.