Evaluation of the total distribution volume of 18F-FBPA in normal tissues of healthy volunteers by non-compartmental kinetic modeling
Evaluation of the total distribution volume of 18F-FBPA in normal tissues of healthy volunteers by non-compartmental kinetic modeling
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DOI：
10.1007/s12149-019-01427-9
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发表时间：
2019-12-05
影响因子：
2.6
通讯作者：
Hatazawa, Jun
中科院分区：
文献类型：
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作者：
Romanov, Victor;Isohashi, Kayako;Hatazawa, Jun
目的硼中子俘获治疗（BNCT）是一种无创的肿瘤放射治疗方法。在BNCT中，如果使用B-10硼- l -苯丙氨酸（B-10- bpa）作为硼载体，则使用4-硼-2-[F-18]-氟- l -苯丙氨酸（F-18- fbpa） PET来估计B-10在靶肿瘤和正常组织中的蓄积。本研究的目的是通过动力学分析来评估健康志愿者正常器官中F-18-FBPA的总分布体积（Vt），并利用所获得的Vt值来估计正常器官中B-10-BPA治疗剂量下的硼浓度。方法6名健康志愿者注射F-18-FBPA (3-5 MBq/kg)，随后进行7次PET-CT扫描。测定注射前、注射后8次全血和血浆中F-18-FBPA的放射性。采用PMOD软件对PET图像进行分析。为每个受试者手工绘制12个感兴趣的体积区域，包括大脑、心脏、右肺、脾脏、肝脏、腮腺唾腺、食管、胃、胰腺、肠和骨髓，并使用Logan图和两个Ichise多线性分析（MA1和MA2）进行分析。较好的模型由多个拟合优度参数和残差分布定义。在得到Vt值后，利用Vt和内插的血浆活性数据，以ppm为单位估算注射后30g b -10- bpa -果糖（B-10-BPA-fr）剂量的硼浓度。结果Ichise MA2模型在所有模型中拟合效果最好。与其他模型（Logan plot平均AIC为31.4，Ichise MA1模型平均AIC为4.2）相比，所有地区Ichise MA2的赤池信息标准（AIC平均值为- 14.0）最低。Ichise MA2模型的平均Vt值为胰腺的0.94 +/- 0.14 ml/ml至右肺的0.16 +/- 0.02 ml/ml。B-10-BPA-fr的估计硼浓度在胰腺中最高（注射后1小时14.0 +/- 1.9 ppm，注射后2小时5.7 +/- 1.7 ppm），在右肺中最低（注射后1小时2.4 +/- 0.3 ppm，注射后2小时1.0 +/- 0.3 ppm）。结论利用F-18-FBPA的Vt值和Ichise多元线性分析2 （MA2）可以较好地估计正常组织中B-10的浓度。临床试验编号：UMIN000022850。
Objective Boron neutron capture therapy (BNCT) is a noninvasive radiation therapy method for cancer treatment. In BNCT, 4-borono-2-[F-18]-fluoro-L-phenylalanine (F-18-FBPA) PET has been employed to estimate B-10 accumulation in target tumors and normal tissues if B-10 borono-L-phenylalanine (B-10-BPA) is used as a boron carrier. The purpose of the current study was to evaluate the total distribution volume (Vt) of F-18-FBPA in normal organs of healthy volunteers by kinetic analysis and to estimate boron concentration in normal organs for the therapeutic dose of B-10-BPA using obtained Vt values. Methods Six healthy volunteers were injected with F-18-FBPA (3-5 MBq/kg), and 7 PET-CT scans were performed subsequently. F-18-FBPA radioactivity in whole blood and plasma was measured before, and eight times after the injection. PET images were analyzed by PMOD software. Twelve volumetric regions of interest including the brain, heart, right lung, spleen, liver, parotid salivary glands, esophagus, stomach, pancreas, intestines, and bone marrow were drawn manually for each subject and analyzed with the Logan plot and two Ichise multilinear analyses (MA1 and MA2). The better model was defined by several goodness-of-fit parameters and residual distribution. After Vt values had been derived, boron concentration was estimated in ppm for the B-10-BPA-fructose (B-10-BPA-fr) dose 30 g 1 and 2 h post-injection using Vt and interpolated plasma activity data. Results The Ichise MA2 model showed the best fit among all models. Akaike Information Criterion (AIC) was the lowest for the Ichise's MA2 in all regions (mean AIC value - 14.0) comparing to the other models (Logan plot mean AIC 31.4; Ichise MA1 model mean AIC - 4.2). Mean Vt values of the Ichise MA2 model ranged from 0.94 +/- 0.14 ml/ml in the pancreas to 0.16 +/- 0.02 ml/ml in the right lung. Estimated boron concentration for B-10-BPA-fr had the highest value in the pancreas (14.0 +/- 1.9 ppm 1 h after, and 5.7 +/- 1.7 ppm 2 h after the F-18-FBPA administration) and the lowest value in the right lung (2.4 +/- 0.3 ppm 1 h, and 1.0 +/- 0.3 ppm 2 h post-injection). Conclusion The B-10 concentration in normal tissues was best estimated using Vt values of F-18-FBPA with the Ichise multilinear analysis 2 (MA2). Trail registry The UMIN clinical trial number: UMIN000022850.