This title appears in the Scientific Report : 2023 
Quantification of [18F]-SynVesT-1 PET using thin-layer chromatography and image derived input function
Foerges, Anna Linea (Corresponding author)
Kroll, Tina / Matusch, Andreas / Neumaier, Bernd / Bauer, Andreas / Drzezga, Alexander / Elmenhorst, David
Nuklearchemie; INM-5
Molekulare Organisation des Gehirns; INM-2
2023
The 29th Annual Meeting of the Organization for Human Brain Mapping, Montréal (Canada), 2023-07-22 - 2023-07-26
Poster
SleepLess - Darstellung synaptischer Plastizität während therapeutischen Schlafentzugs in Depression
Brain Dysfunction and Plasticity
Neuroimaging


Objectives: Synaptic vesicle protein 2A, a marker of synaptic density, can be imaged by [18F]SynVesT 1 positron emission tomography (PET), but quantification requires an arterial input function. An alternative to high-performance liquid chromatography (HPLC) of arterial blood samples can be an input function derived from the dynamic PET images in combination with thin-layer chromatography (TLC)-based analysis of arterialized venous blood. We aimed to quantify synaptic density by obtaining an image derived input function (IDIF) from bilateral internal carotid artery volume of interest (VOI) at the level of the carotid siphon and correcting it for metabolites using a newly developed blood analysis with TLC.Methods: [18F]SynVesT-1 PET list mode (90 min) data and three-dimensional T1-weighted magnetic resonance (MR) data were collected in nine healthy volunteers using an integrated 3 Tesla MR/BrainPET system. Reconstructed PET data (framing schema: 6x 10s, 3x 20s, 3x 30s, 4x 60s, 3x 150s, 15x 300s) and corresponding MR data were realigned, co-registered, segmented and normalized using PMOD Neuro Tool. The first eight normalized PET frames were averaged and filtered (6 mm 3D Gaussian), then, based on this PET image, cubic VOIs were placed over the left and right internal carotid arteries. Subsequently, the 20 hottest connected voxels within each cubic VOI were automatically selected on each side and merged into one VOI, which was transferred to the dynamic PET images to obtain IDIF. Arterialized venous blood samples were collected repeatedly during the PET scan. For blood analysis, aliquots of plasma (400 µl) were mixed with SynVesT 1 cold standard (20 µl, 5µg/ml) and extraction solution (acetonitrile/methanol, 50/50, 800 µl). The mixture was centrifuged and aliquots of supernatants were applied to a TLC plate and developed with a mobile phase of chloroform/methanol/diethylamine (18.4 ml/1.6 ml/40 µl). Whole blood, plasma and pellets were measured in a γ-counter. TLC plates were developed in a Canberra instant imager for 4 h and analysed with the corresponding software. IDIF was scaled [1] using whole blood samples drawn 60, 75 and 90 min after simultaneous injection and scan start to correct for partial volume effects. The scaled IDIF was used to generate a metabolite- and extraction-corrected (derived from blood analysis) plasma input function. These input functions were used to apply the one-tissue compartment model (1TCM) to quantify regional synaptic density in the human brain.Results: Synaptic density was quantified in nine volunteers (4 females) aged 20-45 years (mean: 27.8 ± 9.4) using TLC-based blood analysis, IDIF and the 1TCM. The fraction of radioactivity corresponding to the parent compound was 34 ± 6 % and 31 ± 5 % at 60 min and 90 min after radiotracer injection, respectively. The scaling factor was 1.27 ± 0.20 on average. Mean [18F]SynVesT 1 VT values ranged from 3.64 ± 21.06 mL/cm³ in the centrum semiovale to 20.90 ± 3.87 ml/cm³ in the Heschl’s gyrus. Estimated K1 ranged from 0.303 ±0.065 ml/min/cm³ (centrum semiovale) to 1.163 ± 0.270 ml/min/cm³ (Heschl’s gyrus) and the k2 estimates ranged from 0.040 ± 0.010 (amygdala) to 0.112 ± 0.024 (pons).Conclusion: The parent fraction of radioactivity at 60 min after radiotracer injection was slightly higher compared to HPLC-based results [2]. Estimated VT values were similar to those reported previously [2], whereas K1 and k2 values were higher. Our preliminary data suggest that IDIF with bilateral VOI over the internal carotid artery in combination with TLC-based blood analysis may be an alternative to arterial input functions for quantification of synaptic density using [18F]SynVesT-1 PET in human brains.References:[1] He X. et al. (2020), `Image-derived input functions for quantification of A1 adenosine receptors availability in mice brains using PET and [18F]CPFPX´, Frontiers in Physiology, vol. 29, no. 10, pp. 1617.[2] Naganawa M. et al. (2021), `First-in-human evaluation of (18)F-SynVesT-1, a novel radioligand for PET imaging of synaptic vesicle protein 2A´, Journal of Nuclear Medicine, vol. 62, no. 4, pp. 561-567.