Enhanced tumor detection using a folate receptor-targeted near-infrared fluorochrome conjugate

被引:101
作者
Moon, WK [1 ]
Lin, YH [1 ]
O'Loughlin, T [1 ]
Tang, Y [1 ]
Kim, DE [1 ]
Weissleder, R [1 ]
Tung, CH [1 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA
关键词
D O I
10.1021/bc0340114
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:539 / 545
页数:7
相关论文
共 39 条
  • [1] Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging
    Achilefu, S
    Dorshow, RB
    Bugaj, JE
    Rajagopalan, R
    [J]. INVESTIGATIVE RADIOLOGY, 2000, 35 (08) : 479 - 485
  • [2] Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands
    Becker, A
    Hessenius, C
    Licha, K
    Ebert, B
    Sukowski, U
    Semmler, W
    Wiedenmann, B
    Grötzinger, C
    [J]. NATURE BIOTECHNOLOGY, 2001, 19 (04) : 327 - 331
  • [3] Prediction of binding constants of protein ligands: A fast method for the prioritization of hits obtained from de novo design or 3D database search programs
    Bohm, HJ
    [J]. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1998, 12 (04) : 309 - 323
  • [4] In vivo molecular target assessment of matrix metalloproteinase inhibition
    Bremer, C
    Tung, CH
    Weissleder, R
    [J]. NATURE MEDICINE, 2001, 7 (06) : 743 - 748
  • [5] Imaging of differential protease expression in breast cancers for detection of aggressive tumor phenotypes
    Bremer, C
    Tung, CH
    Bogdanov, A
    Weissleder, R
    [J]. RADIOLOGY, 2002, 222 (03) : 814 - 818
  • [6] Optical imaging of matrix metalloproteinase-2 activity in tumors: Feasibility study in a mouse model
    Bremer, C
    Bredow, S
    Mahmood, U
    Weissleder, R
    Tung, CH
    [J]. RADIOLOGY, 2001, 221 (02) : 523 - 529
  • [7] Guo WJ, 1999, J NUCL MED, V40, P1563
  • [8] Near-infrared optical imaging of the breast with model-based reconstruction
    Jiang, HB
    Iftimia, NV
    Xu, Y
    Eggert, JA
    Fajardo, LL
    Klove, KL
    [J]. ACADEMIC RADIOLOGY, 2002, 9 (02) : 186 - 194
  • [9] Biodistribution of a 153Gd-folate dendrimer, generation=4, in mice with folate-receptor positive and negative ovarian tumor xenografts
    Konda, SD
    Wang, S
    Brechbiel, M
    Wiener, EC
    [J]. INVESTIGATIVE RADIOLOGY, 2002, 37 (04) : 199 - 204
  • [10] Specific targeting of folate-dendrimer MRI contrast agents to the high affinity fo late receptor expressed in ovarian tumor xenografts
    Konda, SD
    Aref, M
    Wang, S
    Brechbiel, M
    Wiener, EC
    [J]. MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE, 2001, 12 (2-3) : 104 - 113