Hematologic toxicity, although often transient, is the most common limiting adverse effect during somatostatin peptide receptor radionuclide therapy. This study investigated the association between Monte Carlo–derived absorbed dose to the red marrow (RM) and hematologic toxicity in patients being treated for their neuroendocrine tumors. Methods: Twenty patients each receiving 4 treatment cycles of [¹⁷⁷Lu]Lu-DOTATATE were included. Multiple-time-point ¹⁷⁷Lu SPECT/CT imaging–based RM dosimetry was performed using an artificial intelligence–driven workflow to segment vertebral spongiosa within the field of view (FOV). This workflow was coupled with an in-house macroscale/microscale Monte Carlo code that incorporates a spongiosa microstructure model. Absorbed dose estimates to RM in lumbar and thoracic vertebrae within the FOV, considered as representations of the whole-body RM absorbed dose, were correlated with hematologic toxicity markers at about 8 wk after each cycle and at 3- and 6-mo follow-up after completion of all cycles. Results: The median of absorbed dose to RM in lumbar and thoracic vertebrae within the FOV (D_{median,vertebrae}) ranged from 0.019 to 0.11 Gy/GBq. The median of cumulative absorbed dose across all 4 cycles was 1.3 Gy (range, 0.6–2.5 Gy). Hematologic toxicity was generally mild, with no grade 2 or higher toxicity for platelets, neutrophils, or hemoglobin. However, there was a decline in blood counts over time, with a fractional value relative to baseline at 6 mo of 74%, 97%, 57%, and 97%, for platelets, neutrophils, lymphocytes, and hemoglobin, respectively. Statistically significant correlations were found between a subset of hematologic toxicity markers and RM absorbed doses, both during treatment and at 3- and 6-mo follow-up. This included a correlation between the platelet count relative to baseline at 6-mo follow up: D_{median,vertebrae} (r = –0.64, P = 0.015), D_{median,lumbar} (r = –0.72, P = 0.0038), D_{median,thoracic} (r = –0.58, P = 0.029), and D_{average,vertebrae} (r = –0.66, P = 0.010), where D_{median,lumbar} and D_{median,thoracic} are median absorbed dose to the RM in the lumbar and thoracic vertebrae, respectively, within the FOV and D_{average,vertebrae} is the mass-weighted average absorbed dose of all vertebrae. Conclusion: This study found a significant correlation between image-derived absorbed dose to the RM and hematologic toxicity, including a relative reduction of platelets at 6-mo follow up. These findings indicate that absorbed dose to the RM can potentially be used to understand and manage hematologic toxicity in peptide receptor radionuclide therapy.

血液学毒性虽然通常是短暂的，但却是生长抑素肽受体放射性核素治疗期间最常见的限制性不良反应。本研究调查了蒙特卡罗衍生的红骨髓 (RM) 吸收剂量与接受神经内分泌肿瘤治疗的患者的血液毒性之间的关联。方法：纳入20 名患者，每人接受 4 个 [ ¹⁷⁷ Lu]Lu-DOTATATE治疗周期。使用人工智能驱动的工作流程进行基于多时间点¹⁷⁷ Lu SPECT/CT 成像的 RM 剂量测定，以在视场 (FOV) 内分割椎骨海绵体。该工作流程与内部宏观/微观蒙特卡罗代码相结合，其中包含海绵体微观结构模型。 FOV 内腰椎和胸椎 RM 吸收剂量估计值（被视为全身 RM 吸收剂量的代表）与每个周期后约 8 周以及 3 个月和 6 个月随访时的血液学毒性标志物相关完成所有周期后。结果：视场内腰椎和胸椎的 RM 吸收剂量中位数（D_{中位数，椎骨}）范围为 0.019 至 0.11 Gy/GBq。所有 4 个周期的累积吸收剂量中位数为 1.3 Gy（范围：0.6-2.5 Gy）。血液学毒性一般较轻微，对血小板、中性粒细胞或血红蛋白无 2 级或更高毒性。然而，随着时间的推移，血细胞计数有所下降，血小板、中性粒细胞、淋巴细胞和血红蛋白相对于 6 个月基线的分数值分别为 74%、97%、57% 和 97%。在治疗期间以及 3 个月和 6 个月的随访中，血液学毒性标志物的子集与 RM 吸收剂量之间发现了统计学上显着的相关性。这包括 6 个月随访时血小板计数相对于基线之间的相关性：D_{中位，椎骨}( r = –0.64，P = 0.015)，D_{中位，腰椎}( r = –0.72，P = 0.0038)，D_{中位，胸椎}（r = –0.58，P = 0.029）和D_{平均，椎骨}（r = –0.66，P = 0.010），其中D_{中位，腰椎}和D_{中位，胸椎}是腰椎 RM 的中位吸收剂量，胸椎分别在FOV和D内_{平均吸收剂量，椎骨}是所有椎骨的质量加权平均吸收剂量。结论：这项研究发现 RM 的图像吸收剂量与血液学毒性之间存在显着相关性，包括 6 个月随访时血小板的相对减少。这些发现表明 RM 的吸收剂量有可能用于了解和管理肽受体放射性核素治疗中的血液毒性。