Univ. Lille, CHU Lille, EA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associees, Lille, France.
Haematology Department, Hôpital Claude Huriez, CHU Lille, F-59000, Lille, France.
Sci Rep. 2018 Oct 5;8(1):14860. doi: 10.1038/s41598-018-33160-0.
Monoclonal antibodies (mAbs) are key components in several therapies for cancer and inflammatory diseases but current knowledge of their clinical pharmacokinetics and distribution in human tissues remains incomplete. Consequently, optimal dosing and scheduling in clinics are affected. With sequential radiolabeled mAb-based imaging, radiation dosing in tissues/organs can be calculated to provide a better assessment of mAb concentrations in tissues. This is the first pharmacokinetic model of Y-Ibritumomab tiuxetan (Y-IT) in humans to be described, based on three-dimensional (3D) dosimetry using single-photon emission computed-tomography coupled with computed-tomography. 19 patients with follicular lymphoma were treated initially with Y-IT in the FIZZ trial. Based on a compartmental approach individualising the vascular compartment within studied organs, this study proposes a reliable pharmacokinetic (PK) five-compartment model replacing the currently used two-compartment model and constitutes a new direction for further research. This model provides exchange constants between the different tissues, Area Under the Curve of In-IT in blood (AUC) and Mean Residence Time (MRT) that have not been reported so far for IT. Finally, the elimination process appears to occur in a compartment other than the liver or the spleen and suggests the metabolism of mAbs may take place mainly on the vascular compartment level.
单克隆抗体（mAbs）是癌症和炎症性疾病的几种治疗方法中的关键组成部分，但目前对其在人体组织中的临床药代动力学和分布的了解仍不完整。因此，临床中的最佳给药和方案安排受到影响。通过连续放射性标记的 mAb 基成像，可以计算组织/器官中的辐射剂量，从而更好地评估 mAb 在组织中的浓度。这是首次基于单光子发射计算机断层扫描与计算机断层扫描相结合的三维（3D）剂量测定法，对人源伊布替莫单抗替昔坦（Y-IT）进行描述的药代动力学模型。19 名滤泡性淋巴瘤患者在 FIZZ 试验中最初接受 Y-IT 治疗。基于个体血管腔室的房室模型方法，该研究提出了一个可靠的药代动力学（PK）五房室模型，取代了目前使用的两房室模型，为进一步研究提供了新的方向。该模型提供了不同组织之间的交换常数、血液中 In-IT 的曲线下面积（AUC）和平均驻留时间（MRT），这些参数迄今为止尚未报告过。最后，消除过程似乎发生在肝脏或脾脏之外的其他腔室中，这表明 mAbs 的代谢可能主要发生在血管腔室水平上。
