Enhanced tumor detection using a folate receptor-targeted near-infrared fluorochrome conjugate
Enhanced tumor detection using a folate receptor-targeted near-infrared fluorochrome conjugate
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DOI：
10.1021/bc0340114
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发表时间：
2003-05-01
影响因子：
4.7
通讯作者：
Tung, CH
中科院分区：
文献类型：
--
作者：
Moon, WK;Lin, YH;Tung, CH
目前正在开发荧光光学成像技术，以在体内成像特定的分子靶标。检测技术的范围从提供微观细节到具有潜在临床用途的全身成像系统。最近已经开发了许多靶特异性近红外成像探针来对受体、抗原和酶进行成像。本研究的目的是评估一种新的近红外（NIR）叶酸受体（FR）靶向成像探针，以提高FR阳性癌症的检测能力。我们假设叶酸的修饰将保留体内受体亲和力，尽管体积较大的NIR荧光染料NIR 2（em = 682 nm）。与FR阴性人纤维肉瘤HT 1080细胞相比，FR阳性鼻咽表皮样癌KB细胞对NIR缀合物的细胞摄取显著更高。当肿瘤植入体内时，与HT 1080肿瘤相比，相同大小的KB肿瘤显示出高2.4倍的信号强度（24小时）。在KB肿瘤中，在24 h观察到最大信号背景比（3倍）。在类似条件下，注射未改性的NIR 2荧光染料不会导致持续的对比度增加。此外，用NIR 2-叶酸探针的肿瘤增强持续超过48小时，并且通过施用未标记的叶酸在体内是可恢复的。这些结果表明，叶酸修饰的NIR荧光染料缀合物可用于改善FR阳性肿瘤的检测。
Fluorescence optical imaging technologies are currently being developed to image specific molecular targets in vivo. Detection technologies range from those providing microscopic detail to whole body imaging systems with potential clinical use. A number of target-specific near-infrared imaging probes have recently been developed to image receptors, antigens, and enzymes. The goal of the current study was to evaluate a new near-infrared (NIR) folate receptor (FR)-targeted imaging probe for its ability to improve detection of FR-positive cancers. We hypothesized that modification of folate would retain receptor affinity in vivo, despite the bulkier NIR fluorochrome, NIR2 (em = 682 nm). Cellular uptake of the NIR conjugates was significantly higher in FR-positive nasopharyngeal epidermoid carcinoma, KB cells, compared to FR-negative human fibrosarcoma, HT1080 cells. When tumors were implanted in vivo, equal-sized KB tumors showed a 2.4-fold higher signal intensity compared to HT1080 tumors (24 h). The maximum signal-to-background ratio (3-fold) was observed at 24 h in KB tumor. Injection of the unmodified NIR2 fluorochrome did not result in persistent contrast increases under similar conditions. Furthermore, tumor enhancement with the NIR2-folate probe persisted over 48 h and was inhibitable in vivo by administration of unlabeled folate. These results indicate that folate-modified NIR fluorochrome conjugate can be used for improved detection of FR-positive tumors.