Noninvasive quantification of [18F]SynVesT-1 binding using simplified reference tissue model 2,European Journal of Nuclear Medicine and Molecular Imaging

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Noninvasive quantification of [18F]SynVesT-1 binding using simplified reference tissue model 2
European Journal of Nuclear Medicine and Molecular Imaging ( IF 8.6 ) Pub Date : 2024-08-19 , DOI: 10.1007/s00259-024-06885-6
Mika Naganawa ₁ , Jean-Dominique Gallezot ₁ , Songye Li ₁ , Nabeel B Nabulsi ₁ , Shannan Henry ₁ , Zhengxin Cai ₁ , David Matuskey _{1,

2,

3} , Yiyun Huang ₁ , Richard E Carson ₁

Affiliation

Purpose

[¹⁸F]SynVesT-1, a positron emission tomography (PET) radiotracer for the synaptic vesicle glycoprotein 2A (SV2A), demonstrates kinetics similar to [¹¹C]UCB-J, with high brain uptake, fast kinetics fitting well with the one-tissue compartment (1TC) model, and excellent test-retest reproducibility. Challenges arise due to the similarity between k₂ and \(\:{k}_{2}^{{\prime\:}}\) (efflux rate of the reference region), when applying the simplified reference tissue model (SRTM) and related methods in [¹¹C]UCB-J studies to accurately estimate \(\:{k}_{2}^{{\prime\:}}\). This study evaluated the suitability of these methods to estimate [¹⁸F]SynVesT-1 binding using centrum semiovale (CS) or cerebellum (CER) as reference regions.

Method

Seven healthy participants underwent 120-min PET scans on the HRRT scanner with [¹⁸F]SynVesT-1. Six participants underwent test and retest scans. Arterial blood sampling and metabolite analysis provided input functions for the 1TC model, serving as the gold standard for kinetic parameters values. SRTM, coupled SRTM (SRTMC) and SRTM2 estimated were applied to estimate \(\:{BP}_{\text{ND}}\)(ref: CS) and DVR_CER(ref: CER) values. For SRTM2, the population average of \(\:{k}_{2}^{{\prime\:}}\) was determined from the 1TC model applied to the reference region. Test-retest variability and minimum scan time were also calculated.

Results

The 1TC k₂ (1/min) values for CS and CER were 0.031 ± 0.004 and 0.021 ± 0.002, respectively. Although SRTMC \(\:{k}_{2}^{{\prime\:}}\) was much higher than 1TC \(\:{k}_{\text{2}}\), SRTMC underestimated BP_ND(ref: CS) and DVR_CER by an average of 3% and 1% across regions, respectively, due to similar bias in k₂ and \(\:{k}_{2}^{{\prime\:}}\) estimation. SRTM underestimated BP_ND(ref: CS) by an average of 3%, but with the CER as reference region, SRTM estimation was unstable and DVR_CER underestimation varied by region (mean 10%). Using population average \(\:{k}_{2}^{{\prime\:}}\) values, SRTM2 BP_ND and DVR_CER showed the best agreement with 1TC estimates.

Conclusion

Our findings support the use of population \(\:{k}_{2}^{{\prime\:}}\) value in SRTM2 with [¹⁸F]SynVesT-1 for the estimation of \(\:{BP}_{\text{ND}}\) or DVR_CER, regardless of the choice of reference region.

中文翻译：

使用简化的参考组织模型 2 对 [18F]SynVesT-1 结合进行无创定量

目的

[ ¹⁸ F]SynVesT-1 是一种突触小泡糖蛋白 2A (SV2A) 的正电子发射断层扫描 (PET) 放射性示踪剂，其动力学特性与 [ ¹¹ C]UCB-J 相似，具有高脑摄取、快速动力学特性，与-组织室（1TC）模型，以及出色的重测重现性。当应用_简化的参考组织模型（SRTM ）和 [ ¹¹ C]UCB-J 研究中的相关方法来准确估计\(\:{k}_{2}^{{\prime\:}}\) 。本研究评估了这些方法使用半卵圆中心 (CS) 或小脑 (CER) 作为参考区域估计 [ ¹⁸ F]SynVesT-1 结合的适用性。

方法

七名健康参与者在 HRRT 扫描仪上使用 [ ¹⁸ F]SynVesT-1 接受了 120 分钟的 PET 扫描。六名参与者接受了测试和重新测试扫描。动脉血采样和代谢物分析为1TC模型提供了输入函数，作为动力学参数值的金标准。 SRTM、耦合 SRTM (SRTMC) 和 SRTM2 估计被应用于估计\(\:{BP}_{\text{ND}}\) （参考：CS）和DVR _CER （参考：CER）值。对于 SRTM2， \(\:{k}_{2}^{{\prime\:}}\)的总体平均值是根据应用于参考区域的 1TC 模型确定的。还计算了重测变异性和最短扫描时间。

结果

CS 和 CER 的 1TC k ₂ (1/min) 值分别为 0.031 ± 0.004 和 0.021 ± 0.002。虽然 SRTMC \(\:{k}_{2}^{{\prime\:}}\)远高于 1TC \(\:{k}_{\text{2}}\) ，但 SRTMC 低估了BP由于k ₂和\(\:{k}_{2}^{{\prime\:}中的类似偏差， _ND （参考：CS）和DVR _CER跨区域平均分别为 3% 和 1% }\)估计。 SRTM 平均低估BP _ND （参考：CS）3%，但以 CER 作为参考区域，SRTM 估计不稳定， DVR _CER低估因区域而异（平均 10%）。使用总体平均\(\:{k}_{2}^{{\prime\:}}\)值，SRTM2 BP _ND和DVR _CER显示与 1TC 估计值最一致。