Sgouros George, Hobbs Robert F, Song Hong
Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, MD 21231, USA.
Curr Radiopharm. 2011 Jul;4(3):261-5. doi: 10.2174/1874471011104030261.
As a consequence of the high potency and short range of alpha-particles, radiopharmaceutical therapy with alpha- particle emitting radionuclides is a promising treatment approach that is under active pre-clinical and clinical investigation. To understand and predict the biological effects of alpha-particle radiopharmaceuticals, dosimetry is required at the micro or multi-cellular scale level. At such a scale, highly non-uniform irradiation of the target volume may be expected and the utility of a single absorbed dose value to predict biological effects comes into question. It is not currently possible to measure the pharmacokinetic input required for micro scale dosimetry in humans. Accordingly, pre-clinical studies are required to provide the pharmacokinetic data for dosimetry calculations. The translation of animal data to the human requires a pharmacokinetic model that links macro- and micro-scale pharmacokinetics thereby enabling the extrapolation of micro-scale kinetics from macroscopic measurements. These considerations along with a discussion of the appropriate physical quantity and related units for alpha-particle radiopharmaceutical therapy are examined in this review.
由于α粒子的高能量和短射程，使用发射α粒子的放射性核素进行放射性药物治疗是一种很有前景的治疗方法，目前正处于积极的临床前和临床研究阶段。为了理解和预测α粒子放射性药物的生物学效应，需要在微观或多细胞尺度水平上进行剂量测定。在这样的尺度下，预计靶体积会受到高度不均匀的照射，因此用单一吸收剂量值来预测生物学效应的实用性受到质疑。目前还无法测量人体微观尺度剂量测定所需的药代动力学输入。因此，需要进行临床前研究以提供用于剂量计算的药代动力学数据。将动物数据转化为人体数据需要一个药代动力学模型，该模型将宏观和微观尺度的药代动力学联系起来，从而能够从宏观测量中推断出微观尺度的动力学。本综述探讨了这些考虑因素以及α粒子放射性药物治疗的适当物理量和相关单位。
