Single-time-point tumor dosimetry using population-based model selection and nonlinear mixed-effects modeling in [177Lu]Lu-PSMA-617 therapy

IF 3.2 2区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Medical physics Pub Date : 2025-09-18 DOI:10.1002/mp.70000

Deni Hardiansyah, Elham Yousefzadeh-Nowshahr, Indra Budiansah, Ursula Nemer, Ade Riana, Felix Kind, Ambros J. Beer, Philipp T. Meyer, Gerhard Glatting, Michael Mix

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引用次数: 0

Abstract

Background

Molecular radiotherapy with [¹⁷⁷Lu]Lu-PSMA-617 is an effective treatment for metastatic castration-resistant prostate cancer. Accurate dosimetry is essential for maximizing therapeutic efficacy while minimizing toxicity. However, standard dosimetry requires multiple imaging sessions, posing logistical challenges. Single-time-point (STP) dosimetry offers a practical alternative but remains challenging for tumor kinetics due to high inter-patient variability. Nonlinear mixed-effects (NLME) modeling, combined with population-based model selection (PBMS), has demonstrated potential for improving STP dosimetry accuracy.

Purpose

The purpose of this study was to evaluate the accuracy of STP tumor dosimetry using SPECT/CT data, PBMS, and an NLME model in a large population with diverse biokinetic measurements for [¹⁷⁷Lu]Lu-PSMA-617 therapy.

Methods

Biokinetic data for [¹⁷⁷Lu]Lu-PSMA-617 in tumors were obtained from forty-nine patients with metastatic castration-resistant prostate cancer using SPECT/CT at time points (1.80 ± 0.80), (18.67 ± 0.90), (42.63 ± 1.03), (66.27 ± 0.96), and (159.02 ± 23.35) h after injection. Ten different functions, derived from various parameterizations of two- to four-exponential functions, were fitted to the data using the NLME framework. Each function's parameters were defined as a combination of fixed and random effects. A PBMS approach was employed, using goodness-of-fit tests and Akaike weights to identify the function best supported by the data. The selected function from the NLME fitting of all time points with the leave-one-out method was used to calculate the reference time-integrated activities per volume (TIAVs). The parameters from STP fitting were used to calculate the STP TIAVs. Additionally, STP dosimetry was performed using the Hänscheid method to calculate the TIAVs. Relative deviations (RDs) and root-mean-square errors (RMSEs) were used to analyse the accuracy of the calculated STP TIAVs and Hänscheid method TIAVs compared with the reference TIAVs.

Results

The function $f_{4 b} (t) = A_{1} e^{- (λ_{1} + λ_{phys}) t} + A_{2} e^{- (λ_{phys}) t} - (A_{1} + A_{2}) e^{- (λ_{2} + λ_{phys}) t}$ was selected as the fit function most supported by the data with an Akaike weight of 93%. For STP dosimetry, a single SPECT/CT measurement at time point 4 (66.3 ± 0.9 h) after injection showed a relatively low mean RD of 0.5% ± 11.0% and median RD of -0.6%. The RMSEs for the STP TIAVs RDs for time points 1–5 were 53%, 29%, 17%, 11%, and 38%, respectively. The STP tumor dosimetry using the PBMS NLME method outperformed the Hänscheid method for all investigated time points.

Conclusion

Our findings demonstrate that a single SPECT/CT measurement at 3 days after injection may be used to estimate tumor TIAVs in [¹⁷⁷Lu]Lu-PSMA-617 therapy using the NLME method and PBMS.

Abstract Image

查看原文本刊更多论文

在[177Lu]Lu-PSMA-617治疗中使用基于人群的模型选择和非线性混合效应建模的单时间点肿瘤剂量测定。

背景：分子放射治疗[177Lu]Lu-PSMA-617是转移性去势抵抗性前列腺癌的有效治疗方法。准确的剂量测定是必不可少的，以最大限度地提高治疗效果，同时尽量减少毒性。然而，标准剂量法需要多次成像，这给后勤带来了挑战。单时间点（STP）剂量法提供了一种实用的替代方案，但由于患者之间的高度可变性，对肿瘤动力学仍然具有挑战性。非线性混合效应（NLME）模型与基于种群的模型选择（PBMS）相结合，已经证明了提高STP剂量测定精度的潜力。目的：本研究的目的是评估STP肿瘤剂量测定的准确性，使用SPECT/CT数据，PBMS和NLME模型在具有不同生物动力学测量的大型人群中用于[177Lu]Lu-PSMA-617治疗。方法：对49例转移性去雄抵抗性前列腺癌患者，在注射后（1.80±0.80）、（18.67±0.90）、（42.63±1.03）、（66.27±0.96）、（159.02±23.35）h，应用SPECT/CT获取[177Lu] lu - psm -617在肿瘤中的生物动力学数据。10个不同的函数，从各种参数化的二至四指数函数，拟合数据使用NLME框架。每个函数的参数被定义为固定效应和随机效应的组合。采用PBMS方法，使用拟合优度检验和赤池权值来识别数据最支持的函数。利用留一法对所有时间点的NLME拟合所选择的函数计算参考时间积分每体积活动（TIAVs）。利用STP拟合得到的参数计算STP tiav。此外，STP剂量法使用Hänscheid方法计算tiav。采用相对偏差（RDs）和均方根误差（rmse）对STP计算的tiav和Hänscheid方法tiav与参考tiav的精度进行了分析。结果:函数f 4 b (t) = 1 e -(λ1 +λphy) t + 2 e -(λphy) t - (1 + 2) e -(λ2 +λphy) t $ {{f} _ {4 {\ mathrm {b }}}}\ ( {\ mathrm {t }} ) = {{{\ mathrm{一}}}_1}\ {{{\ mathrm {e }}}^{ - ( {{{{{\ λ}}}_1}+{{{{\λ}}}_ {{\ mathrm {phy}}}}}) {\ mathrm {t }}}} + {{{\ mathrm{一}}}\ mathrm _2} {{{{e }}}^{ - ( {{{{{\ λ}}}_ {{\ mathrm {phy}}}}}) {\ mathrm {t }}}} - ( {{{{\ mathrm{一}}}_1}+ {{{\ mathrm{一}}}_2}}{{{\ mathrm {e }}}^{ - ( {{{{{\ λ}}}_2}+{{{{\lambda}}}_{{\mathrm{phys}}}}}){\mathrm{t}}}}$作为数据最支持的拟合函数，赤似权值为93%。对于STP剂量测定，注射后时间点4（66.3±0.9 h）的单次SPECT/CT测量显示相对较低的平均RD为0.5%±11.0%，中位RD为-0.6%。STP TIAVs rd在1 ~ 5时间点的rmse分别为53%、29%、17%、11%和38%。使用PBMS NLME方法的STP肿瘤剂量测定在所有研究时间点上都优于Hänscheid方法。结论：我们的研究结果表明，注射后3天的单次SPECT/CT测量可用于估计[177Lu]Lu-PSMA-617治疗中使用NLME方法和PBMS的肿瘤TIAVs。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medical physics 医学-核医学

CiteScore

6.80

自引率

15.80%

发文量

660

审稿时长

1.7 months

期刊介绍： Medical Physics publishes original, high impact physics, imaging science, and engineering research that advances patient diagnosis and therapy through contributions in 1) Basic science developments with high potential for clinical translation 2) Clinical applications of cutting edge engineering and physics innovations 3) Broadly applicable and innovative clinical physics developments Medical Physics is a journal of global scope and reach. By publishing in Medical Physics your research will reach an international, multidisciplinary audience including practicing medical physicists as well as physics- and engineering based translational scientists. We work closely with authors of promising articles to improve their quality.