Laboratory of Experimental Surgical Oncology, Department of Surgery, Erasmus MC, Rotterdam, The Netherlands
Departments of Nuclear Medicine and Radiology, Erasmus MC, Rotterdam, The Netherlands.
J Nucl Med. 2016 Apr;57(4):601-7. doi: 10.2967/jnumed.115.166173. Epub 2015 Dec 30.
Liposomal chemotherapy offers several advantages over conventional therapies, including high intratumoral drug delivery, reduced side effects, prolonged circulation time, and the possibility to dose higher. The efficient delivery of liposomal chemotherapeutics relies, however, on the enhanced permeability and retention (EPR) effect, which refers to the ability of macromolecules to extravasate leaky tumor vessels and accumulate in the tumor tissue. Using a panel of human xenograft tumors, we evaluated the influence of the EPR effect on liposomal distribution in vivo by injection of pegylated liposomes radiolabeled with (111)In. Liposomal accumulation in tumors and organs was followed over time by SPECT/CT imaging. We observed that fast-growing xenografts, which may be less representative of tumor development in patients, showed higher liposomal accumulation than slow-growing xenografts. Additionally, several other parameters known to influence the EPR effect were evaluated, such as blood and lymphatic vessel density, intratumoral hypoxia, and the presence of infiltrating macrophages. The investigation of various parameters showed a few correlations. Although hypoxia, proliferation, and macrophage presence were associated with tumor growth, no hard conclusions or predictions could be made regarding the EPR effect or liposomal uptake. However, liposomal uptake was significantly correlated with tumor growth, with fast-growing tumors showing a higher uptake, although no biological determinants could be elucidated to explain this correlation.
脂质体化疗相对于传统疗法具有许多优势，包括高肿瘤内药物递送、降低副作用、延长循环时间和增加剂量的可能性。然而，脂质体化疗药物的有效递送依赖于增强的通透性和保留（EPR）效应，这是指大分子渗出渗漏肿瘤血管并在肿瘤组织中积累的能力。我们使用一组人异种移植肿瘤，通过注射用 (111)In 标记的聚乙二醇化脂质体来评估 EPR 效应对体内脂质体分布的影响。通过 SPECT/CT 成像，我们观察了随时间推移脂质体在肿瘤和器官中的积累情况。我们观察到，生长较快的异种移植瘤可能不太代表患者的肿瘤发展，其脂质体积累高于生长较慢的异种移植瘤。此外，还评估了其他几个已知影响 EPR 效应的参数，如血管和淋巴管密度、肿瘤内缺氧和浸润性巨噬细胞的存在。对各种参数的研究表明存在一些相关性。尽管缺氧、增殖和巨噬细胞存在与肿瘤生长相关，但对于 EPR 效应或脂质体摄取，无法得出明确的结论或预测。然而，脂质体摄取与肿瘤生长显著相关，生长较快的肿瘤摄取量较高，尽管无法阐明生物学决定因素来解释这种相关性。
