基于全身药代动力学模型的靶向放射性核素治疗的生物学效应。
The biological effectiveness of targeted radionuclide therapy based on a whole-body pharmacokinetic model.
机构信息
Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, 1111 Highland Ave, Madison, WI 53705, USA.
出版信息
Phys Med Biol. 2010 Oct 7;55(19):5723-34. doi: 10.1088/0031-9155/55/19/007. Epub 2010 Sep 8.
Biologically effective dose (BED) may be more of a relevant quantity than absorbed dose for establishing tumour response relationships. By taking into account the dose rate and tissue-specific parameters such as repair and radiosensitivity, it is possible to compare the relative biological effects of different targeted radionuclide therapy (TRT) agents. The aim of this work was to develop an analytical tumour BED calculation for TRT that could predict a relative biological effect based on normal body and tumour pharmacokinetics. This work represents a step in the direction of establishing relative pharmacokinetic criteria of when the BED formalism is more applicable than absorbed dose for TRT. A previously established pharmacokinetic (PK) model for TRT was used and adapted into the BED formalism. An analytical equation for the protraction factor, which incorporates dose rate and repair rate, was derived. Dose rates within the normal body and tumour were related to the slopes of their time-activity curves which were determined by the ratios of their respective PK parameters. The relationships between the tumour influx-to-efflux ratio (k(34):k(43)), central compartment efflux-to-influx ratio (k(12):k(21)), central elimination (k(el)), and tumour repair rate (μ), and tumour BED were investigated. As the k(34):k(43) ratio increases and the k(12):k(21) ratio decreases, the difference between tumour BED and D increases. In contrast, as the k(34):k(43) ratios decrease and the k(12):k(21) ratios increase, the tumour BED approaches D. At large k(34):k(43) ratios, the difference between tumour BED and D increases to a maximum as k(el) increases. At small k(34):k(43) ratios, the tumour BED approaches D at very small k(el). At small μ and small k(34):k(43) ratios, the tumour BED approaches D. For large k(34):k(43) ratios, large μ values cause tumour BED to approach D. This work represents a step in the direction of establishing relative PK criteria of when the BED formalism is more applicable than absorbed dose for TRT. It also provides a framework by which the biological effects of different TRT agents can be compared in order to predict efficacy.
生物有效剂量（BED）可能比吸收剂量更能反映肿瘤的反应关系。通过考虑剂量率和组织特异性参数，如修复和放射敏感性，可以比较不同靶向放射性核素治疗（TRT）药物的相对生物学效应。本工作旨在开发一种可用于预测相对生物学效应的分析性肿瘤 BED 计算方法，该方法基于正常组织和肿瘤的药代动力学。这一工作是朝着建立 BED 公式何时比吸收剂量更适用于 TRT 的相对药代动力学标准迈出的一步。本工作使用了先前建立的 TRT 药代动力学（PK）模型，并将其改编为 BED 公式。推导出了一个包含剂量率和修复率的延长因子的解析方程。正常组织和肿瘤内的剂量率与它们的时间-活性曲线的斜率有关，斜率由各自 PK 参数的比值决定。研究了肿瘤内流入-流出比（k(34):k(43)）、中央室流出-流入比（k(12):k(21)）、中央消除（k(el)）和肿瘤修复率（μ）与肿瘤 BED 之间的关系。随着 k(34):k(43)比值的增加和 k(12):k(21)比值的降低，肿瘤 BED 与 D 的差值增大。相反，随着 k(34):k(43)比值的降低和 k(12):k(21)比值的增加，肿瘤 BED 接近 D。在较大的 k(34):k(43)比值下，随着 k(el)的增加，肿瘤 BED 与 D 的差值增加到最大值。在较小的 k(34):k(43)比值下，肿瘤 BED 在非常小的 k(el)下接近 D。在较小的 μ 和较小的 k(34):k(43)比值下，肿瘤 BED 接近 D。在较大的 k(34):k(43)比值下，较大的 μ 值导致肿瘤 BED 接近 D。本工作是朝着建立 BED 公式何时比吸收剂量更适用于 TRT 的相对 PK 标准迈出的一步。它还提供了一个框架，通过该框架可以比较不同 TRT 药物的生物学效应，以预测疗效。
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