As a result of therapy-induced apoptosis, peripheral blood monocytes are recruited to tumors, where they become tumor-associated macrophages (TAMs). To date, few studies have investigated noninvasive molecular imaging for assessment of macrophage infiltration in response to therapy-induced apoptosis. Here, noninvasive assessment of changes in tumor accumulation of TAMs was proposed as a new way to measure early tumor response to anticancer therapy. Three different nanoparticles, QD710-Dendron quantum dots (QD710-D), Ferumoxytol, and PG-Gd-NIR813, were used for near-infrared fluorescence imaging, T2-weighted magnetic resonance imaging, and dual optical/T1-weighted MR imaging, respectively, in the MDA-MB-435 tumor model. Treatment with Abraxane induced tumor apoptosis and infiltrating macrophages. In spite of markedly different physicochemical properties among the nanoparticles, in vivo imaging revealed increased uptake of all three nanoparticles in Abraxane-treated tumors compared with untreated tumors. Moreover, imaging visualized increased uptake of QD710-D in MDA-MB-435 tumors but not in drug-resistant MDA-MB-435R tumors grown in the mice treated with Abraxane. Our results suggest that infiltration of macrophages due to chemotherapy-induced apoptosis was partially responsible for increased nanoparticle uptake in treated tumors. Noninvasive imaging techniques in conjunction with systemic administration of imageable nanoparticles that are taken up by macrophages are a potentially useful tool for assessing early treatment response.

中文翻译：

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巨噬细胞作为潜在的肿瘤微环境靶标，用于抗癌治疗早期反应的无创成像

由于治疗诱导的凋亡，外周血单核细胞被募集到肿瘤中，在那里它们成为肿瘤相关的巨噬细胞（TAM）。迄今为止，很少有研究调查非侵入性分子成像以评估巨噬细胞浸润对治疗诱导的细胞凋亡的反应。在此，提出了无创评估TAMs肿瘤累积变化的方法，作为测量早期肿瘤对抗癌治疗反应的新方法。将三种不同的纳米粒子QD710-Dendron量子点（QD710-D），Ferumoxytol和PG-Gd-NIR813用于近红外荧光成像，T2加权磁共振成像和双光学/ T1加权MR成像，分别在MDA-MB-435肿瘤模型中。用Abraxane治疗可诱导肿瘤细胞凋亡并浸润巨噬细胞。体内成像显示，与未经治疗的肿瘤相比，在经Abraxane治疗的肿瘤中，所有三种纳米颗粒的摄取均增加。此外，成像显像了在用Abraxane治疗的小鼠中生长的MDA-MB-435肿瘤中QD710-D的摄取增加，但在耐药MDA-MB-435R肿瘤中却没有。我们的研究结果表明，化疗诱导的凋亡导致巨噬细胞浸润部分归因于治疗肿瘤中纳米颗粒摄取的增加。与巨噬细胞摄取的可成像纳米颗粒的全身给药相结合的非侵入性成像技术是评估早期治疗反应的潜在有用工具。