Nonclinical study and applicability of the absorbed dose conversion method with a single biodistribution measurement for targeted alpha-nuclide therapy.
Nonclinical study and applicability of the absorbed dose conversion method with a single biodistribution measurement for targeted alpha-nuclide therapy.
复制标题
单次生物分布测量的吸收剂量转换法用于靶向α核素治疗的非临床研究和适用性。
DOI：
10.1186/s40658-021-00425-z
复制
发表时间：
2021-12-11
期刊：
影响因子：
4
通讯作者：
Ishioka NS
中科院分区：
文献类型：
--
作者：
Sakashita T;Matsumoto S;Watanabe S;Hanaoka H;Ohshima Y;Ikoma Y;Ukon N;Sasaki I;Higashi T;Higuchi T;Tsushima Y;Ishioka NS
我们最近报道了一种新的吸收剂量转换方法，RAP（药代动力学比值），该方法使用单一生物分布测量，即注射剂量/g的百分比。然而，在确定单次测量注射剂量百分比/g的最佳时间时，存在一些数学上的模糊性。因此，我们的目的是在数学上重建RAP方法，并检查单次测量的最佳时机。我们导出了时间t的RAP剂量转换方法的新形式。此外，我们获得了一个公式，用于确定单次测量注射剂量百分比/g的最佳时间，假设生物清除率为单室模型。我们使用具有放射性衰变加权的代表性RAP系数来研究新形式的性能。代表性RAP系数的剂量转换预测真实[2111at]MABG吸收剂量的误差为10%或更小。在注入后4 h绘制的代表性RAP系数的逆曲线（之前的工作中报道的最佳时间）与注入后4 h RAP系数的新逆曲线非常接近。接下来，用物理半衰期分别为7.2 h和10 d的放射性标记化合物对不同生物清除半衰期的最佳时间进行了分析。最佳时间的行为图显示，随着目标生物清除半衰期的增加，趋向于收敛到一个恒定值。当目标生物清除半衰期与参比生物半衰期相等时，两种化合物在5%或10%预测误差内的最佳时间区域分布在最佳时间附近。最后，以[2111at]MABG为例，演示了RAP剂量转换。新形式修正的RAP剂量转换方法能够利用类似的药代动力学，如[131I]MIBG，估算[211At]MABG的吸收剂量。本公式揭示了两种放射性药物吸收剂量转换的最佳成像时间点。需要进一步的分析和临床数据来阐明针对α -核素治疗的单次测量最佳时间的行为图的有效性。在线版本包含补充材料，可在10.1186/s40658-021-00425-z获得。
We recently reported a new absorbed dose conversion method, RAP (RAtio of Pharmacokinetics), for 211At-meta-astatobenzylguanidine (211At-MABG) using a single biodistribution measurement, the percent injected dose/g. However, there were some mathematical ambiguities in determining the optimal timing of a single measurement of the percent injected dose/g. Thus, we aimed to mathematically reconstruct the RAP method and to examine the optimal timing of a single measurement. We derived a new formalism of the RAP dose conversion method at time t. In addition, we acquired a formula to determine the optimal timing of a single measurement of the percent injected dose/g, assuming the one-compartment model for biological clearance. We investigated the new formalism’s performance using a representative RAP coefficient with radioactive decay weighting. Dose conversions by representative RAP coefficients predicted the true [211At]MABG absorbed doses with an error of 10% or less. The inverses of the representative RAP coefficients plotted at 4 h post-injection, which was the optimal timing reported in the previous work, were very close to the new inverses of the RAP coefficients 4 h post-injection. Next, the behavior of the optimal timing was analyzed by radiolabeled compounds with physical half-lives of 7.2 h and 10 d on various biological clearance half-lives. Behavior maps of optimal timing showed a tendency to converge to a constant value as the biological clearance half-life of a target increased. The areas of optimal timing for both compounds within a 5% or 10% prediction error were distributed around the optimal timing when the biological clearance half-life of a target was equal to that of the reference. Finally, an example of RAP dose conversion was demonstrated for [211At]MABG. The RAP dose conversion method renovated by the new formalism was able to estimate the [211At]MABG absorbed dose using a similar pharmacokinetics, such as [131I]MIBG. The present formalism revealed optimizing imaging time points on absorbed dose conversion between two radiopharmaceuticals. Further analysis and clinical data will be needed to elucidate the validity of a behavior map of the optimal timing of a single measurement for targeted alpha-nuclide therapy. The online version contains supplementary material available at 10.1186/s40658-021-00425-z.
登录
查看更多内容
影响因子：
4
作者：
Sato T;Furuta T;Liu Y;Naka S;Nagamori S;Kanai Y;Watabe T
通讯作者：
Watabe T
影响因子：
4
作者：
Ukon N;Zhao S;Washiyama K;Oriuchi N;Tan C;Shimoyama S;Aoki M;Kubo H;Takahashi K;Ito H
通讯作者：
Ito H
影响因子：
9.3
作者：
Zalutsky, Michael R.;Reardon, David A.;Bigner, Darell D.
通讯作者：
Bigner, Darell D.
（44）SC-PSMA-617用于与（177）LU-PSMA-617-preclinical研究相比（68）GA-PSMA-11和（68）GA-PSMA-617的（177）LU-PSMA-617-序列研究。
影响因子：
3.2
作者：
Umbricht CA;Benešová M;Schmid RM;Türler A;Schibli R;van der Meulen NP;Müller C
通讯作者：
Müller C
影响因子：
3.4
作者：
Spetz, Johan;Rudqvist, Nils;Forssell-Aronsson, Eva
通讯作者：
Forssell-Aronsson, Eva