Spring Bryan Q, Palanisami Akilan, Hasan Tayyaba
Massachusetts General Hospital and Harvard Medical School, Wellman Center for Photomedicine, Boston, Massachusetts 02114.
Massachusetts General Hospital and Harvard Medical School, Wellman Center for Photomedicine, Boston, Massachusetts 02114bMassachusetts General Hospital, Department of Dermatology, Boston, Massachusetts 02114cHarvard University and Massachusetts Institute.
J Biomed Opt. 2014 Jun;19(6):066006. doi: 10.1117/1.JBO.19.6.066006.
Molecular-targeted probes are emerging with applications for optical biopsy of cancer. An underexplored potential clinical use of these probes is to monitor residual cancer micrometastases that escape cytoreductive surgery and chemotherapy. Here, we show that leukocytes, or white blood cells, residing in nontumor tissues--as well as those infiltrating micrometastatic lesions--uptake cancer cell-targeted, activatable immunoconjugates nonspecifically, which limits the accuracy and resolution of micrometastasis recognition using these probes. Receiver operating characteristic analysis of freshly excised tissues from a mouse model of peritoneal carcinomatosis suggests that dual-color imaging, adding an immunostain for leukocytes, offers promise for enabling accurate recognition of single cancer cells. Our results indicate that leukocyte identification improves micrometastasis recognition sensitivity and specificity from 92 to 93%--for multicellular metastases >20 to 30 μm in size--to 98 to 99.9% for resolving metastases as small as a single cell.
分子靶向探针正在出现，并应用于癌症的光学活检。这些探针一个尚未充分探索的潜在临床用途是监测那些逃过减瘤手术和化疗的残留癌症微转移灶。在这里，我们表明，存在于非肿瘤组织中的白细胞，以及浸润微转移灶的白细胞，会非特异性摄取癌细胞靶向的、可激活的免疫缀合物，这限制了使用这些探针识别微转移灶的准确性和分辨率。对腹膜癌小鼠模型新鲜切除组织的受试者工作特征分析表明，添加白细胞免疫染色的双色成像有望实现对单个癌细胞的准确识别。我们的结果表明，对于大小>20至30μm的多细胞转移灶，白细胞识别将微转移灶识别的敏感性和特异性从92%提高到93%，对于小至单个细胞的转移灶的分辨，敏感性和特异性提高到98%至99.9%。
