The amount of injected 177Lu-octreotate strongly influences biodistribution and dosimetry in C57BL/6N mice
The amount of injected 177Lu-octreotate strongly influences biodistribution and dosimetry in C57BL/6N mice
复制标题
177Lu-奥曲酸的注射量强烈影响 C57BL/6N 小鼠的生物分布和剂量测定
作者：
E. Schüler;Andreas Österlund;Eva Forssell
背景177 Lu-octreotate疗法已被证明在治疗神经内分泌肿瘤患者后获得了良好的结果。177 Lu-octreotate在肿瘤组织中的结合和摄取一直是关注的焦点，但在正常组织中的生物分布特性仍未完全了解，受体饱和的影响可能是重要的。本研究的目的是研究177 Lu-octreotate的量对177 Lu-octreotate在小鼠正常组织中的生物分布的影响。材料和方法。C57 BL/6 N雌性小鼠静脉内注射0.1-150 MBq 177 Lu-奥曲酸盐（0.039 μg肽/MBq）。注射后0.25 h ~ 14 d，在麻醉状态下通过心脏穿刺处死小鼠。测定血液、骨髓、肾脏、肝脏、肺、胰腺和脾脏中的放射性浓度，并计算平均吸收剂量。结果活性浓度随时间和注入活性量而变化。在注射后4-8小时，发现肝、肺、胰腺和脾的活性浓度局部最大。除了较低的注射活性（0.1-1 MBq）外，在肾脏中发现了总体最高摄取（%IA/g）。注射后4 h，肾内活性浓度为11-23%IA/g，第7天为0.22-1.9%IA/g。此外，在肺、胰腺和脾脏中观察到随着注射活性增加，活性浓度明显降低。结论研究的所有组织中的活性浓度受到注射的177 Lu-octreotate的量的强烈影响。在低剂量（0.1-1 MBq，0.0039-0.039 μg）和中等剂量（5-45 MBq，0.2-1.8 μg）之间，发现每单位注射活性的平均吸收剂量存在较大差异。此外，结果清楚地表明，需要有更好的方法来估计骨髓吸收剂量，而不是基于单一血液样本分析的方法。由于关键器官的吸收剂量将限制177 Lu-奥曲酸盐的给药量，因此在优化此类治疗时必须考虑这些发现。
Background. 177Lu-octreotate therapy has proven to give favorable results after treatment of patients with neuroendocrine tumors. Much focus has been on the binding and uptake of 177Lu-octreotate in tumor tissue, but biodistribution properties in normal tissues is still not fully understood, and the effect of receptor saturation may be important. The aim of this study was to investigate the influence of the amount of 177Lu-octreotate on the biodistribution of 177Lu-octreotate in normal tissues in mice. Material and methods. C57BL/6N female mice were intravenously injected with 0.1–150 MBq 177Lu-octreotate (0.039 μg peptide/MBq). The mice were killed 0.25 h to 14 days after injection by cardiac puncture under anesthesia. Activity concentration was determined in blood, bone marrow, kidneys, liver, lungs, pancreas, and spleen, and mean absorbed doses were calculated. Results. The activity concentration varied with time and amount of injected activity. At 4–8 h after injection, a local maximum in activity concentration was found for liver, lungs, pancreas, and spleen. With the exception for the lower injected activities (0.1–1 MBq), the overall highest uptake was found in the kidneys (%IA/g). Large variations were found and the activity concentration in kidneys was 11–23%IA/g at 4 h, and 0.22–1.9%IA/g at 7 days after injection. Furthermore, a clear reduction in activity concentration with increased injected activity was observed for lungs, pancreas and spleen. Conclusion. The activity concentration in all tissues investigated was strongly influenced by the amount of 177Lu-octreotate injected. Large differences in mean absorbed dose per unit injected activity were found between low (0.1–1 MBq, 0.0039–0.039 μg) and moderate amounts (5–45 MBq, 0.2–1.8 μg). Furthermore, the results clearly showed the need for better ways to estimate absorbed dose to bone marrow other than methods based on a single blood sample analysis. Since the absorbed dose to critical organs will limit the amount of 177Lu-octreotate administered, these findings must be taken into consideration when optimizing this type of therapy.