Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room B3B69, MSC1088, Bethesda, MD 20892-1088, USA.
BMC Cancer. 2012 Aug 8;12:345. doi: 10.1186/1471-2407-12-345.
Near infrared (NIR) photoimmunotherapy (PIT) is a new type of cancer treatment based on a monoclonal antibody (mAb)-NIR phthalocyanine dye, (IR700) conjugate. In vitro cancer-specific cell death occurs during NIR light exposure in cells previously incubated with mAb-IR700 conjugates. However, documenting rapid cell death in vivo is more difficult.
A luciferase-transfected breast cancer cell (epidermal growth factor receptor+, MDA-MB-468luc cells) was produced and used for both in vitro and in vivo experiments for monitoring the cell killing effect of PIT. After validation of cytotoxicity with NIR exposure up to 8 J/cm2in vitro, we employed an orthotopic breast cancer model of bilateral MDA-MB-468luc tumors in female athymic mice, which subsequently received a panitumumab-IR700 conjugate in vivo. One side was used as a control, while the other was treated with NIR light of dose ranging from 50 to 150 J/cm2. Bioluminescence imaging (BLI) was performed before and after PIT.
Dose-dependent cell killing and regrowth was successfully monitored by the BLI signal in vitro. Although tumor sizes were unchanged, BLI signals decreased by >95% immediately after PIT in vivo when light intensity was high (>100 J/cm2), however, in mice receiving lower intensity NIR (50 J/cm2), tumors recurred with gradually increasing BLI signal.
PIT induced massive cell death of targeted tumor cells immediately after exposure of NIR light that was demonstrated with BLI in vivo.
近红外（NIR）光免疫疗法（PIT）是一种基于单克隆抗体（mAb）-NIR 酞菁染料（IR700）缀合物的新型癌症治疗方法。在先前用 mAb-IR700 缀合物孵育的细胞中，在 NIR 光照射下会发生体外特异性癌细胞死亡。然而，更难在体内记录快速的细胞死亡。
生成了一种转染荧光素酶的乳腺癌细胞（表皮生长因子受体阳性，MDA-MB-468luc 细胞），并用于体外和体内实验，以监测 PIT 的细胞杀伤作用。在体外用 NIR 照射至 8 J/cm2 验证细胞毒性后，我们使用双侧 MDA-MB-468luc 肿瘤的原位乳腺癌模型，随后在雌性无胸腺小鼠体内给予 panitumumab-IR700 缀合物。一侧用作对照，另一侧用 50 至 150 J/cm2 剂量的 NIR 光治疗。在 PIT 前后进行生物发光成像（BLI）。
在体外，通过 BLI 信号成功监测了剂量依赖性的细胞杀伤和再生长。尽管肿瘤大小没有变化，但在体内当光强度较高（>100 J/cm2）时，PIT 后立即通过 BLI 信号观察到肿瘤几乎完全丧失，然而，在接受较低强度 NIR（50 J/cm2）的小鼠中，肿瘤复发，BLI 信号逐渐增加。
PIT 在体内用 BLI 立即诱导靶向肿瘤细胞的大量细胞死亡。
