Dassanayake Praveen, Anazodo Udunna C, Liu Linshan, Narciso Lucas, Iacobelli Maryssa, Hicks Justin, Rusjan Pablo, Finger Elizabeth, St Lawrence Keith
Department of Medical Biophysics, University of Western Ontario, London, ON, Canada.
Lawson Health Research Institute, 268 Grosvenor St, London, ON, N6A 4V2, Canada.
EJNMMI Res. 2023 Jan 12;13(1):1. doi: 10.1186/s13550-023-00950-1.
The purpose of this study was to assess the feasibility of using a minimally invasive simultaneous estimation method (SIME) to quantify the binding of the 18-kDa translocator protein tracer [F]FEPPA. Arterial sampling was avoided by extracting an image-derived input function (IDIF) that was metabolite-corrected using venous blood samples. The possibility of reducing scan duration to 90 min from the recommended 2-3 h was investigated by assuming a uniform non-displaceable distribution volume (V) to simplify the SIME fitting.
SIME was applied to retrospective data from healthy volunteers and was comprised of both high-affinity binders (HABs) and mixed-affinity binders (MABs). Estimates of global V and regional total distribution volume (V) from SIME were not significantly different from values obtained using a two-tissue compartment model (2CTM). Regional V estimates were greater for HABs compared to MABs for both the 2TCM and SIME, while the SIME estimates had lower inter-subject variability (41 ± 17% reduction). Binding potential (BP) values calculated from regional V and brain-wide V estimates were also greater for HABs, and reducing the scan time from 120 to 90 min had no significant effect on BP. The feasibility of using venous metabolite correction was evaluated in a large animal model involving a simultaneous collection of arterial and venous samples. Strong linear correlations were found between venous and arterial measurements of the blood-to-plasma ratio and the remaining [F]FEPPA fraction. Lastly, estimates of BP and the specific distribution volume (i.e., V = V - V) from a separate group of healthy volunteers (90 min scan time, venous-scaled IDIFs) agreed with estimates from the retrospective data for both genotypes.
The results of this study demonstrate that accurate estimates of regional V, BP and V can be obtained by applying SIME to [F]FEPPA data. Furthermore, the application of SIME enabled the scan time to be reduced to 90 min, and the approach worked well with IDIFs that were scaled and metabolite-corrected using venous blood samples.
本研究的目的是评估使用微创同步估计方法（SIME）来量化18 kDa转运蛋白示踪剂[F]FEPPA结合的可行性。通过提取经静脉血样代谢物校正的图像衍生输入函数（IDIF）避免了动脉采样。通过假设均匀的不可置换分布容积（V）来简化SIME拟合，研究了将扫描时间从推荐的2 - 3小时缩短至90分钟的可能性。
SIME应用于健康志愿者的回顾性数据，其中包括高亲和力结合物（HAB）和混合亲和力结合物（MAB）。SIME得出的总体V和区域总分布容积（V）估计值与使用双组织室模型（2CTM）获得的值无显著差异。对于2CTM和SIME，HAB的区域V估计值均高于MAB，而SIME估计值的受试者间变异性较低（降低了41±17%）。由区域V和全脑V估计值计算出的结合潜力（BP）值对于HAB也更高，并且将扫描时间从120分钟减少到90分钟对BP没有显著影响。在一个涉及同时采集动脉和静脉样本的大型动物模型中评估了使用静脉代谢物校正的可行性。在血 - 血浆比率和剩余[F]FEPPA分数的静脉和动脉测量之间发现了强线性相关性。最后，来自另一组健康志愿者（扫描时间90分钟，静脉缩放的IDIF）的BP和特定分布容积（即V = V - V）估计值与两种基因型回顾性数据的估计值一致。
本研究结果表明，通过将SIME应用于[F]FEPPA数据，可以获得区域V、BP和V的准确估计值。此外，SIME的应用使扫描时间能够缩短至90分钟，并且该方法与使用静脉血样进行缩放和代谢物校正的IDIF配合良好。
