Background: The accumulation of liposome encapsulated chemotherapy in solid cancers is dependent on the presence of the enhanced permeability and retention (EPR) effect. Positron emission tomography (PET) imaging with a liposome encapsulated radioisotope, such as liposome encapsulated Cu-64 (⁶⁴Cu-liposome) may help to identify tumors with high liposome accumulation, and thereby stratify patients based on expected benefit from liposomal chemotherapy. However, intravenous administration of liposomes without a cytotoxic content is complicated by the accelerated blood clearance (ABC) phenomenon for succeeding therapeutic liposome dosing. Alternative markers for assessing the tumor’s EPR level are therefore warranted.
Materials and Methods: To increase our understanding of EPR variations and to ultimately identify an alternative marker for the EPR effect, we investigated the correlation between ⁶⁴Cu-liposome PET/CT (EPR effect) and ⁶⁸Ga-RGD PET/CT (neoangiogenesis), ¹⁸F-FDG PET/CT (glycolysis), diffusion-weighted MRI (diffusivity) and interstitial fluid pressure in two experimental cancer models (CT26 and COLO 205).
Results: ⁶⁴Cu-liposome and ⁶⁸Ga-RGD SUV_max displayed a significant moderate correlation, however, none of the other parameters evaluated displayed significant correlations. These results indicate that differences in neoangiogenesis may explain some EPR variability, however, as correlations were only moderate and not observed for SUV_mean, ⁶⁸Ga-RGD is probably insufficient to serve as a stand-alone surrogate marker for quantifying the EPR effect and stratifying patients.



中文翻译：

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64Cu-脂质体增强渗透性和保留效应的无创分子成像：与 68Ga-RGD、流体压力、扩散率和 18F-FDG 的体内相关性

背景：脂质体包裹的化学疗法在实体癌中的积累取决于增强渗透性和保留（EPR）效应的存在。使用脂质体包裹的放射性同位素（例如脂质体包裹的 Cu-64（⁶⁴ Cu-脂质体））进行正电子发射断层扫描 (PET) 成像可能有助于识别具有高脂质体积累的肿瘤，从而根据脂质体化疗的预期益处对患者进行分层。然而，没有细胞毒性成分的脂质体的静脉内给药由于用于后续治疗性脂质体给药的加速血液清除 (ABC) 现象而变得复杂。因此，需要用于评估肿瘤 EPR 水平的替代标志物。
材料和方法：为了增加我们对 EPR 变化的理解并最终确定 EPR 效应的替代标记，我们研究了⁶⁴ Cu-脂质体 PET/CT（EPR 效应）和⁶⁸ Ga-RGD PET/CT（新血管生成）、¹⁸ F- FDG PET/CT（糖酵解）、弥散加权 MRI（弥散性）和两个实验性癌症模型（CT26 和 COLO 205）中的间质液压力。
结果： ⁶⁴ Cu-脂质体和⁶⁸ Ga-RGD SUV _max显示出显着的中等相关性，但是，评估的其他参数均未显示出显着的相关性。这些结果表明，新血管生成的差异可以解释一些 EPR 变异性，然而，由于相关性仅为中等且未观察到 SUV_平均值，⁶⁸ Ga-RGD 可能不足以用作量化 EPR 效应和分层的独立替代标记耐心。