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Background <p>The synaptic vesicle glycoprotein 2&#xa0;A (SV2A) has been identified as a biomarker of interest for neurological pathology. The SV2A specific radiotracer [<sup>18</sup>F]SynVesT-1 has shown good binding characteristics in mouse and human. The aim of this study was to characterize the binding parameters of [<sup>18</sup>F]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 [<sup>18</sup>F]SynVesT-1. Varying concentrations of non-radioactive SynVesT-1 were injected in an increasing mass dose paradigm (<i>n</i> = 21 ) with radioactivity in arterial blood recorded throughout. The radiometabolism was characterized in a further group (<i>n</i> = 7). The total volume of distribution (<i>V</i><sub><i>T</i></sub>) was estimated using compartmental modelling and Logan plot and then compared to the standardized uptake value at 30–60&#xa0;min (<i>SUV</i><sub><i>30 − 60</i></sub>). Occupancy plots and a Lassen plot were generated.</p> Results <p>The pharmacokinetics of [<sup>18</sup>F]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 <i>V</i><sub><i>T</i></sub> was highly correlated with Logan <i>V</i><sub><i>T</i></sub>, as was the <i>SUV</i><sub><i>30 − 60</i></sub>. The <i>V</i><sub><i>ND</i></sub> was estimated to be 3.75, which is 12.5% (pons) to 22% (thalamus) of the <i>V</i><sub><i>T</i></sub>. The estimated upper mass limit required to achieve 5% target occupancy is 0.48&#xa0;µg/kg.</p> Conclusion <p>[<sup>18</sup>F]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 (&lt; 5% occupancy). Data showed no suitable reference region for [<sup>18</sup>F]SynVesT-1, however <i>SUV</i><sub><i>30 − 60</i></sub> does give an appropriate surrogate for <i>V</i><sub><i>T</i></sub>.</p> Clinical trial number <p>Not applicable.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月18日

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  • Catriona Wimberley,
  • Carlos J. Alcaide-Corral,
  • Timaeus E. F. Morgan,
  • Mark G. Macaskill,
  • Bernadette Andrews,
  • Holly McErlain,
  • Valeria K. Burianova,
  • Andrew Sutherland,
  • Adriana A. S. Tavares

摘要

Background

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.

Results

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.

Conclusion

[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.

Clinical trial number

Not applicable.