Background/Objectives:Accurate absorbed dose estimation is essential for optimising targeted radionuclide therapy (TRT) in metastatic castration-resistant prostate cancer, where kidney toxicity is dose-limiting. [177Lu]Lu-rhPSMA-10.1 is a novel PSMA-targeted radioligand with favourable tumour-to-kidney uptake ratios; however, inter-patient pharmacokinetic variability can lead to differences in organ and tumour absorbed doses under fixed-activity administration. Personalised dosimetry offers a means to address this variability. This work aims to create mouse PBPK model-based digital twins for [177Lu]Lu-rhPSMA-10.1 to test the model’s resistance to noise and evaluate its impact on accuracy and absorbed dose calculations.Methods:Five CB-17 SCID mice bearing LNCaP tumour xenografts received 2.6–3.1 MBq [177Lu]Lu-rhPSMA-10.1 intravenously. Biodistribution was assessed 24 h post-injection by organ weighing and gamma counting. The PBPK model, implemented in MATLAB SimBiology (R2023a), was fitted to individual biodistribution data using mouse-specific physiological parameters. Digital twins—combining the model with fitted parameters—were used to generate time–activity curves (TACs) for kidneys, tumours, and the whole body. Gaussian noise (σ= 0–0.35) was added to TACs to simulate measurement error. The model was refitted, and absorbed doses from time-integrated activities (TIAs) were compared to digital twin references.Results:The digital twin approach reproduced experimental data with physiologically plausible parameters. Absorbed dose estimates remained consistent and robust, deviating by <2.3% in kidneys and <1.0% in tumours.Conclusions:PBPK-based digital twins enable reliable, individualised dosimetry, even under substantial measurement uncertainty.
背景/目的：在转移性去势抵抗性前列腺癌的靶向放射性核素治疗中，肾脏毒性是剂量限制因素，因此准确的吸收剂量估算对优化治疗至关重要。[¹⁷⁷Lu]Lu-rhPSMA-10.1是一种新型前列腺特异性膜抗原靶向放射性配体，具有优越的肿瘤-肾脏摄取比；然而，患者间药代动力学差异可能导致固定活度给药方案下器官与肿瘤吸收剂量的不同。个体化剂量测定为应对这种差异性提供了解决方案。本研究旨在建立基于小鼠生理药代动力学模型的[¹⁷⁷Lu]Lu-rhPSMA-10.1数字孪生体，以测试模型对噪声的抗干扰能力，并评估其对剂量计算准确性的影响。 方法：五只携带LNCaP肿瘤异种移植物的CB-17 SCID小鼠经静脉注射2.6–3.1 MBq [¹⁷⁷Lu]Lu-rhPSMA-10.1。注射24小时后通过器官称重和γ计数评估生物分布。采用MATLAB SimBiology（R2023a）构建的生理药代动力学模型，结合小鼠特异性生理参数对个体生物分布数据进行拟合。将模型与拟合参数结合形成的数字孪生体用于生成肾脏、肿瘤及全身的时间-活度曲线。通过添加高斯噪声（σ=0–0.35）模拟测量误差，重新拟合模型后，将时间积分活度推算的吸收剂量与数字孪生体参考值进行比较。 结果：数字孪生体方法以符合生理特征的参数重现了实验数据。吸收剂量估算结果保持稳定可靠，肾脏剂量偏差<2.3%，肿瘤剂量偏差<1.0%。 结论：基于生理药代动力学模型的数字孪生体即使在显著测量不确定度下，仍能实现可靠的个体化剂量测定。
肿瘤(癌症)患者之家