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肽受体放射性核素治疗的个性化辐射剂量测定——究竟需要多少次扫描?

Personalized radiation dosimetry for PRRT-how many scans are really required?

作者信息

Freedman Nanette, Sandström Mattias, Kuten Jonathan, Shtraus Natan, Ospovat Inna, Schlocker Albert, Even-Sapir Einat

机构信息

Institute of Nuclear Medicine, Tel Aviv Sourasky Medical Center, 6 Weizman Street, 64239, Tel Aviv, Israel.

Section of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

出版信息

EJNMMI Phys. 2020 May 11;7(1):26. doi: 10.1186/s40658-020-00293-z.

Abstract

PURPOSE

Over recent years, peptide receptor radiotherapy (PRRT) has been recognized as an effective treatment for patients with metastatic neuroendocrine tumors (NETs). Personalized dosimetry can contribute to improve the outcome of peptide receptor radiotherapy (PRRT) in patients with metastatic NETs. Dosimetry can aid treatment planning, ensuring that absorbed dose to vulnerable normal organs (kidneys and bone marrow) does not exceed safe limits over serial treatments, and that absorbed dose to tumor is sufficient. Absorbed dose is estimated from a series of post-treatment SPECT/CT images. Total self-dose is proportional to the integral under the time activity concentration curve (TACC). Method dependence of image-based absorbed dose calculations has been previously investigated, and we set out here to extend previous work by examining implications of number of data points in the TACC and the numerical integration methods used in estimating absorbed dose.

METHODS

In this retrospective study, absorbed dose estimates and effective half-lives were calculated by fitting curves to TACCs for normal organs and tumors in 30 consecutive patients who underwent a series of 4 post-treatment SPECT/CT scans at 4 h, 24 h, 4-5 days, and 1 week following Lu-DOTATATE PRRT. We examined the effects of including only 2 or 3 rather than all 4 data points in the TACC, and the effect of numerical integration method (mono-exponential alone or in combination with trapezoidal rule) on the absorbed dose and half-life estimates. Our current method is the combination of trapezoidal rule over the first 24 h, with mono-exponential fit thereafter extrapolated to infinity. The other methods were compared to this current method.

RESULTS

Differences in absorbed dose and effective half-life between the current method and estimates based only on the second, third, and fourth scans were very small (mean differences < 2.5%), whereas differences between the current method and 4-point mono-exponential fit were higher (mean differences < 5%) with a larger range. It appears that in a 4-point mono-exponential fit the early (4 h) time point may skew results, causing some large errors. Differences between the current method and values based on only 2 time points were relatively small (mean differences < 3.5%) when the 24 h and 1 week scans were used, but when the 24 h and 4-5 days scans, or the 4-5 days and 1 week scans were used, differences were greater.

CONCLUSION

This study indicates that for Lu-DOTATATE PRRT, accurate estimates of absorbed dose for organs and tumors may be estimated from scans at 24 h, 72 h, and 1 week post-treatment without an earlier scan. It may even be possible to cut out the 72 h scan, though the uncertainty increases. However, further work on more patients is required to validate this.

摘要

目的

近年来,肽受体放射治疗(PRRT)已被公认为是转移性神经内分泌肿瘤(NETs)患者的一种有效治疗方法。个体化剂量测定有助于改善转移性NETs患者的肽受体放射治疗(PRRT)效果。剂量测定可辅助治疗计划制定,确保在系列治疗过程中,对脆弱正常器官(肾脏和骨髓)的吸收剂量不超过安全限值,且对肿瘤的吸收剂量足够。吸收剂量通过一系列治疗后SPECT/CT图像进行估算。总自吸收剂量与时间-活度浓度曲线(TACC)下的积分成正比。此前已对基于图像的吸收剂量计算的方法依赖性进行了研究,我们在此着手通过研究TACC中数据点数量以及估算吸收剂量时所用的数值积分方法的影响来扩展先前的工作。

方法

在这项回顾性研究中,对30例连续患者进行了4次治疗后SPECT/CT扫描,分别在镥-奥曲肽PRRT后的4小时、24小时、4 - 5天和1周,通过将曲线拟合到正常器官和肿瘤的TACC来计算吸收剂量估计值和有效半衰期。我们研究了在TACC中仅纳入2个或3个而非全部4个数据点的影响,以及数值积分方法(仅单指数法或与梯形法则联合)对吸收剂量和半衰期估计值的影响。我们目前的方法是在前24小时采用梯形法则,此后采用单指数拟合并外推至无穷大。将其他方法与当前方法进行比较。

结果

当前方法与仅基于第二次、第三次和第四次扫描的估计值之间的吸收剂量和有效半衰期差异非常小(平均差异<2.5%),而当前方法与4点单指数拟合之间的差异更大(平均差异<5%),范围也更大。似乎在4点单指数拟合中,早期(4小时)时间点可能会使结果产生偏差,导致一些较大误差。当使用24小时和1周扫描时,当前方法与仅基于2个时间点的值之间的差异相对较小(平均差异<3.5%),但当使用24小时和4 - 5天扫描,或4 - 5天和1周扫描时,差异更大。

结论

本研究表明,对于镥-奥曲肽PRRT,在不进行早期扫描的情况下,可通过治疗后24小时、72小时和1周的扫描来准确估算器官和肿瘤的吸收剂量。甚至有可能省去72小时扫描,尽管不确定性会增加。然而,需要对更多患者进行进一步研究以验证这一点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3087/7214583/1534658a1f1e/40658_2020_293_Fig1_HTML.jpg

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