Centre for Health Effects of Radiological and Chemical Agents, College of Health, Medicine and Life Sciences, Brunel University London, Kingston Lane, Uxbridge, London UB8 3PH, United Kingdom of Great Britain and Northern Ireland.
Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast BT9 7AE, United Kingdom of Great Britain and Northern Ireland.
Nucl Med Biol. 2022 Mar-Apr;106-107:10-20. doi: 10.1016/j.nucmedbio.2021.12.002. Epub 2021 Dec 13.
Radium-223 dichloride ([Ra]RaCl), a radiopharmaceutical that delivers α-particles to regions of bone metastatic disease, has been proven to improve overall survival of men with metastatic castration resistant prostate cancer (mCRPC). mCRPC patients enrolled on the ADRRAD clinical trial are treated with a mixed field exposure comprising radium-223 (Ra) and intensity modulated radiotherapy (IMRT). While absorbed dose estimation is an important step in the characterisation of wider systemic radiation risks in nuclear medicine, uncertainties remain for novel radiopharmaceuticals such as Ra.
24-Colour karyotyping was used to quantify the spectrum of chromosome aberrations in peripheral blood lymphocytes of ADRRAD patients at incremental times during their treatment. Dicentric equivalent frequencies were used in standard models for estimation of absorbed blood dose. To account for the mixed field nature of the treatment, existing models were used to determine the ratio of the component radiation types. Additionally, a new approach (M-FISH), based on the ratio of cells containing damage consistent with high-LET exposure (complex chromosomal exchanges) and low-LET exposure (simple exchanges), was used as a pseudo ratio for Ra:IMRT dose.
Total IMRT estimated doses delivered to the blood after completion of mixed radiotherapy (after 37 IMRT fractions and two [Ra]RaCl injections) were in the range of 1.167 ± 0.092 and 2.148 ± 0.096 Gy (dose range across all models applied). By the last treatment cycle analysed in this study (four [Ra]RaCl injections), the total absorbed Ra dose to the blood was estimated to be between 0.024 ± 0.027 and 0.665 ± 0.080 Gy, depending on the model used. Differences between the models were observed, with the observed dose variance coming from inter-model as opposed to inter-patient differences. The M-FISH model potentially overestimates the Ra absorbed blood dose by accounting for further PBL exposure in the vicinity of metastatic sites.
The models presented provide initial estimations of cumulative dose received during incremental IMRT fractions and [Ra]RaCl injections, which will enable improved understanding of the doses received by individual patients. While the M-FISH method builds on a well-established technique for external exposures, further consideration is needed to evaluate this method and its use in assessing non-targeted exposure by Ra after its localization at bone metastatic sites.
镭-223 二氯化物([Ra]RaCl)是一种放射性药物，可将 α 粒子递送至骨转移疾病区域，已被证明可改善转移性去势抵抗性前列腺癌(mCRPC)患者的总生存期。参加 ADRRAD 临床试验的 mCRPC 患者接受混合场照射治疗，包括镭-223(Ra)和强度调制放疗(IMRT)。虽然吸收剂量估计是核医学中更广泛全身辐射风险特征的重要步骤，但对于新型放射性药物(如 Ra)仍存在不确定性。
使用 24 色染色体显带技术，在 ADRRAD 患者接受治疗的各个时间点，定量检测外周血淋巴细胞中的染色体畸变谱。双着丝粒当量频率用于标准模型中估计吸收的血液剂量。为了说明治疗的混合场性质，使用现有的模型来确定辐射类型的组成比例。此外，还使用了一种新方法（M-FISH），基于与高 LET 暴露（复杂染色体交换）和低 LET 暴露（简单交换）一致的损伤细胞比例，作为 Ra:IMRT 剂量的伪比。
混合放疗完成后(接受 37 次 IMRT 分次和 2 次[Ra]RaCl 注射)，血液中接受的总 IMRT 估计剂量在 1.167±0.092 和 2.148±0.096 Gy 之间(应用所有模型的剂量范围)。在本研究分析的最后一个治疗周期(4 次[Ra]RaCl 注射)中，血液中吸收的 Ra 总剂量估计在 0.024±0.027 和 0.665±0.080 Gy 之间，具体取决于所使用的模型。模型之间存在差异，观察到的剂量差异来自于模型之间的差异，而不是患者之间的差异。M-FISH 模型通过考虑转移部位附近的 PBL 进一步暴露，可能高估了 Ra 吸收的血液剂量。
所提出的模型提供了在递增的 IMRT 分次和[Ra]RaCl 注射期间接受的累积剂量的初步估计，这将有助于更好地了解个体患者接受的剂量。虽然 M-FISH 方法建立在外部暴露的成熟技术基础上，但需要进一步考虑该方法及其在评估 Ra 定位在骨转移部位后非靶向暴露中的应用。
