Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
Z Med Phys. 2023 Feb;33(1):82-90. doi: 10.1016/j.zemedi.2022.10.001. Epub 2022 Nov 12.
In radionuclide therapy, activity kinetics in tissues determine the absorbed doses administered and thus efficacy and side effects of treatment. The objective of this work was to derive expressions for the parameters affecting the absorbed dose to a target tissue for first-order activity kinetics. The activity uptake results from contributions from the first-pass activity flow through the target tissue preceding systemic equilibration and uptake after distribution of the administered compound in the body. The absorbed dose from uptake after equilibration is the product of the mean energy deposited per decay in the target tissue, the time integral of the plasma activity concentration, the plasma volume flow per unit target tissue mass, the probability of activity removal during passage, and the mean lifetime of activity in the target tissue. Quantitative analysis of the determinants of absorbed dose exemplarily for radioiodine therapy indicates that the high uptake often observed in Graves' disease must be associated with high tissue perfusion and removal probability and that administration of stable iodine increases mean lifetime. For therapies with long residence times of the active compound in the blood, such as radioiodine therapy, the contribution of the first-pass is small compared with uptake after equilibration. The relative first-pass contribution is higher for agents that are rapidly eliminated from the blood pool, such as radiolabelled somatostatin analogues, and may dominate after arterial application. Understanding the determining parameters in radionuclide therapy reveals dose-limiting factors and opens up opportunities to optimise and individualize therapy, potentially improving treatment success rates.
在放射性核素治疗中，组织中的放射性活度动力学决定了所给予的吸收剂量，从而影响治疗的效果和副作用。本工作的目的是推导出影响靶向组织吸收剂量的参数表达式，用于一级动力学的放射性活度。放射性活度的摄取来源于在全身达到平衡之前通过靶向组织的首过放射性活度流动以及在体内给予的化合物分布后的摄取的贡献。在达到平衡后的摄取产生的吸收剂量是靶组织中每个放射性衰变平均沉积能量、血浆放射性活度浓度时间积分、单位靶组织质量的血浆体积流量、通过过程中放射性活度去除的概率以及靶组织中放射性活度的平均寿命的乘积。放射性碘治疗的吸收剂量决定因素的定量分析表明，Graves 病中经常观察到的高摄取必须与高组织灌注和去除概率相关，并且稳定碘的给予会增加平均寿命。对于在血液中具有长活性化合物居留时间的治疗方法，例如放射性碘治疗，与平衡后摄取相比，首过的贡献较小。对于从血池快速清除的药物（如放射性标记的生长抑素类似物），相对首过贡献更高，并且可能在动脉应用后占主导地位。了解放射性核素治疗中的决定因素揭示了剂量限制因素，并为优化和个体化治疗提供了机会，有可能提高治疗成功率。
