在放射性药物治疗中，肿瘤内放射性的吸收通常导致吸收剂量分布不均匀。治疗成功的可能性可以通过肿瘤控制概率（TCP）来估计，这需要精确的剂量测定，估计单个肿瘤细胞每单位活性的吸收剂量率。方法：用数字放射自显影技术评估用[177Lu]Lu-PSMA-617处理的前列腺癌细胞系LNCaP的异种移植冷冻切片，并用苏木精和伊红染色。数字放射自显影图像用于定义吸收剂量的蒙特卡罗模拟中的源，染色切片用于检测细胞核的位置，以将肿瘤内吸收剂量异质性与细胞密度联系起来。对 225Ac、177Lu 和 90Y 进行了模拟。计算 TCP 是为了估计高 TCP 所需的平均注入活性。生成了主要在肿瘤边界上发生的活动的假设情况并用于模拟吸收剂量。结果：根据染色和模拟结果计算肿瘤细胞每次衰变的吸收剂量，以避免细胞密度低的肿瘤区域中的低吸收剂量低估肿瘤反应。发现 225Ac、177Lu 和 90Y 达到 90% TCP 所需的注入活性平均值为 18.3 kBq（范围，18-22 kBq）、24.3 MBq（范围，20-29 MBq）和 5.6 MBq（范围，5-6 MBq），分别。结论：为了解释由不均匀的肿瘤内活性摄取产生的异质吸收剂量，剂量测定模型可以估计达到治疗反应的足够 TCP 所需的平均活性。这种方法对于准确评估建议的放射性药物治疗的功效是必要的。© 2023，核医学和分子成像协会。

In radiopharmaceutical therapy, intratumoral uptake of radioactivity usually leads to heterogeneous absorbed dose distribution. The likelihood of treatment success can be estimated with the tumor control probability (TCP), which requires accurate dosimetry, estimating the absorbed dose rate per unit activity to individual tumor cells. Methods: Xenograft cryosections of the prostate cancer cell line LNCaP treated with [177Lu]Lu-PSMA-617 were evaluated with digital autoradiography and stained with hematoxylin and eosin. The digital autoradiography images were used to define the source in a Monte Carlo simulation of the absorbed dose, and the stained sections were used to detect the position of cell nuclei to relate the intratumoral absorbed dose heterogeneity to the cell density. Simulations were performed for 225Ac, 177Lu, and 90Y. TCP was calculated to estimate the mean necessary injected activity for a high TCP. A hypothetical case of activity mainly taken up on the tumor borders was generated and used to simulate the absorbed dose. Results: The absorbed dose per decay to tumor cells was calculated from the staining and simulation results to avoid underestimating the tumor response from low absorbed doses in tumor regions with low cell density. The mean of necessary injected activity to reach a 90% TCP for 225Ac, 177Lu, and 90Y was found to be 18.3 kBq (range, 18-22 kBq), 24.3 MBq (range, 20-29 MBq), and 5.6 MBq (range, 5-6 MBq), respectively. Conclusion: To account for the heterogeneous absorbed dose generated from nonuniform intratumoral activity uptake, dosimetry models can estimate the mean necessary activity to reach a sufficient TCP for treatment response. This approach is necessary to accurately evaluate the efficacy of suggested radiopharmaceuticals for therapy.© 2023 by the Society of Nuclear Medicine and Molecular Imaging.