Noninvasive imaging of immune responses.
Noninvasive imaging of immune responses.
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DOI：
10.1073/pnas.1502609112
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发表时间：
2015-05-12
影响因子：
11.1
通讯作者：
Ploegh HL
中科院分区：
文献类型：
--
作者：
Rashidian M;Keliher EJ;Bilate AM;Duarte JN;Wojtkiewicz GR;Jacobsen JT;Cragnolini J;Swee LK;Victora GD;Weissleder R;Ploegh HL
肿瘤常被骨髓源性细胞包围和侵袭。因此，对这些免疫细胞浸润肿瘤的成像可能是检测肿瘤或追踪抗癌治疗反应的一种有吸引力的手段。我们表明，可以通过正电子发射断层扫描（PET）通过它们显示的表面标记来无创地检测这些细胞。在治疗过程中监测免疫反应的能力将有助于早期确定治疗的疗效，并将为决定是否应停止或继续治疗提供信息。因此，无创监测可以改变治疗的应用和评估方式，使许多患者受益。在肿瘤边缘，通常含有中性粒细胞、树突状细胞和活化的巨噬细胞，它们表达II类MHC和CD11b产物。基质细胞、肿瘤细胞和移行细胞（如淋巴细胞）之间的相互作用为免疫反应的无创成像创造了机会。我们开发了羊驼衍生的抗体片段，专门针对小鼠II类MHC和CD11b产品，在多种髓细胞表面表达。我们通过流式细胞术和双光子显微镜验证了这些试剂，以获得细胞分辨率的图像。为了实现对目标细胞群的无创成像，我们开发了一种用18F或64Cu对vhs（骆驼重链抗体的可变结构域（VH））进行定点特异性标记的方法。放射标记的vhh迅速清除循环（t1/2≈20分钟），淋巴器官清晰可见。我们使用vhs来探索异种和同种肿瘤模型中炎症成像的可能性，结果发现肿瘤具有显著的特异性。我们还对注射完全弗氏佐剂后骨髓细胞的浸润进行了成像。抗II类MHC和抗cd11b vhs检测炎症均具有极好的特异性。鉴于vhs易于制造和标记，我们相信这种方法可以改变抗肿瘤反应和/或感染事件的跟踪方式。
Tumors are often surrounded and invaded by bone marrow-derived cells. Imaging the infiltration of such immune cells into tumors may therefore be an attractive means of detecting tumors or of tracking the response to anticancer therapy. We show that it is possible to detect these cells noninvasively by positron emission tomography (PET) via the surface markers displayed by them. The ability to monitor the immune response in the course of therapy will enable early determination of the efficacy of treatment and will inform decisions as to whether treatment should be stopped or continued. Noninvasive monitoring could therefore change how therapies are applied and assessed, to the benefit of many patients. At their margins, tumors often contain neutrophils, dendritic cells, and activated macrophages, which express class II MHC and CD11b products. The interplay between stromal cells, tumor cells, and migratory cells such as lymphocytes creates opportunities for noninvasive imaging of immune responses. We developed alpaca-derived antibody fragments specific for mouse class II MHC and CD11b products, expressed on the surface of a variety of myeloid cells. We validated these reagents by flow cytometry and two-photon microscopy to obtain images at cellular resolution. To enable noninvasive imaging of the targeted cell populations, we developed a method to site-specifically label VHHs [the variable domain (VH) of a camelid heavy-chain only antibody] with 18F or 64Cu. Radiolabeled VHHs rapidly cleared the circulation (t1/2 ≈ 20 min) and clearly visualized lymphoid organs. We used VHHs to explore the possibility of imaging inflammation in both xenogeneic and syngeneic tumor models, which resulted in detection of tumors with remarkable specificity. We also imaged the infiltration of myeloid cells upon injection of complete Freund’s adjuvant. Both anti-class II MHC and anti-CD11b VHHs detected inflammation with excellent specificity. Given the ease of manufacture and labeling of VHHs, we believe that this method could transform the manner in which antitumor responses and/or infectious events may be tracked.
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影响因子：
15
作者：
Blackman, Melissa L.;Royzen, Maksim;Fox, Joseph M.
通讯作者：
Fox, Joseph M.
影响因子：
56.9
作者：
GRUSBY, MJ;JOHNSON, RS;GLIMCHER, LH
通讯作者：
GLIMCHER, LH
影响因子：
14.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.1101046108
发表时间：
2011-07-12
影响因子：
11.1
作者：
Chen, Irwin;Dorr, Brent M.;Liu, David R.
通讯作者：
Liu, David R.
DOI：
10.1073/pnas.90.14.6444
发表时间：
1993-07-15
影响因子：
11.1
作者：
HOLLIGER, P;PROSPERO, T;WINTER, G
通讯作者：
WINTER, G