Personalized dose-based treatment planning requires accurate and reproducible noninvasive measurements to ensure safety and effectiveness. Dose estimation using SPECT is possible but challenging for alpha (α)-particle–emitting radiopharmaceutical therapy (α-RPT) because of complex -emission spectra, extremely low counts, and various image-degrading artifacts across a plethora of scanner–collimator configurations. Through the incorporation of physics-based considerations and skipping of the potentially lossy voxel-based reconstruction step, a recently developed projection-domain low-count quantitative SPECT (LC-QSPECT) method has the potential to provide reproducible, accurate, and precise activity concentration and dose measures across multiple scanners, as is typically the case in multicenter settings. To assess this potential, we conducted an in silico imaging trial to evaluate the LC-QSPECT method for a ²²³Ra-based α-RPT, with the trial recapitulating patient and imaging system variabilities. Methods: A virtual imaging trial titled In Silico Imaging Trial for Quantitation Accuracy (ISIT-QA) was designed with the objectives of evaluating the performance of the LC-QSPECT method across multiple scanner–collimator configurations and comparing performance with a conventional reconstruction–based quantification method. In this trial, we simulated 280 realistic virtual patients with bone-metastatic castration-resistant prostate cancer treated with ²²³Ra-based α-RPT. The trial was conducted with 9 simulated SPECT scanner–collimator configurations. The primary objective of this trial was to evaluate the reproducibility of dose estimates across multiple scanner–collimator configurations using LC-QSPECT by calculating the intraclass correlation coefficient. Additionally, we compared the reproducibility and evaluated the accuracy of both considered quantification methods across multiple scanner–collimator configurations. Finally, the repeatability of the methods was evaluated in a test–retest study. Results: In this trial, data from 268 ²²³RaCl₂ treated virtual prostate cancer patients, with a total of 2,903 lesions, were used to evaluate LC-QSPECT. LC-QSPECT provided dose estimates with good reproducibility across the 9 scanner–collimator configurations (intraclass correlation coefficient > 0.75) and high accuracy (ensemble average values of recovery coefficients ranged from 1.00 to 1.02). Compared with conventional reconstruction-based quantification, LC-QSPECT yielded significantly improved reproducibility across scanner–collimator configurations, accuracy, and test–retest repeatability ($$P < 0.01)$$. Conclusion: LC-QSPECT provides reproducible, accurate, and repeatable dose estimations in ²²³Ra-based α-RPT as evaluated in ISIT-QA. These findings provide a strong impetus for multicenter clinical evaluations of LC-QSPECT in dose quantification for α-RPTs.

基于剂量的个性化治疗计划需要准确且可重复的无创测量，以确保安全性和有效性。使用 SPECT 进行剂量估计是可能的，但对于 α (α) 粒子发射放射性药物治疗 (α-RPT) 来说具有挑战性，因为复杂的发射光谱、极低的计数以及大量扫描仪-准直器配置中的各种图像退化伪影。通过结合基于物理的考虑因素并跳过潜在有损的基于体素的重建步骤，最近开发的投影域低计数定量 SPECT (LC-QSPECT) 方法有可能提供可重复、准确和精确的活性浓度跨多个扫描仪进行剂量测量，这在多中心环境中是典型的情况。为了评估这种潜力，我们进行了一项计算机成像试验，以评估基于²²³ Ra 的 α-RPT 的 LC-QSPECT 方法，该试验概括了患者和成像系统的变异性。方法：设计了一项名为“计算机成像定量准确性试验”(ISIT-QA) 的虚拟成像试验，其目的是评估 LC-QSPECT 方法在多个扫描仪-准直器配置中的性能，并将性能与传统的基于重建的定量进行比较。方法。在这项试验中，我们模拟了 280 名患有骨转移去势抵抗性前列腺癌的真实虚拟患者，他们接受了基于²²³ Ra 的 α-RPT 治疗。该试验使用 9 个模拟 SPECT 扫描仪-准直器配置进行。该试验的主要目的是通过计算组内相关系数，评估使用 LC-QSPECT 的多个扫描仪-准直器配置的剂量估计的再现性。此外，我们还比较了多种扫描仪-准直器配置中两种考虑的量化方法的再现性并评估了准确性。最后，在重测研究中评估了这些方法的可重复性。结果：在本试验中，使用来自 268 ²²³名经RaCl ₂治疗的虚拟前列腺癌患者（总共 2,903 个病灶）的数据来评估 LC-QSPECT。 LC-QSPECT 提供的剂量估计在 9 种扫描仪-准直器配置中具有良好的再现性（组内相关系数 > 0.75），并且精度高（恢复系数的整体平均值范围为 1.00 至 1.02）。与传统的基于重建的量化相比，LC-QSPECT 显着提高了扫描仪-准直器配置的再现性、准确性和重测重复性（$$P < 0.01)$$。结论： LC-QSPECT 在 ISIT-QA 中评估的基于²²³ Ra 的 α-RPT中提供了可重复、准确且可重复的剂量估计。这些发现为 LC-QSPECT 在 α-RPT 剂量定量方面的多中心临床评估提供了强大的推动力。