Journal
MOLECULAR CANCER THERAPEUTICS
Volume 8, Issue 1, Pages 232-239Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-08-0862
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Funding
- Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research
- NATIONAL CANCER INSTITUTE [ZIABC010656, ZIABC010657] Funding Source: NIH RePORTER
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Imaging with labeled monoclonal antibodies may be useful in detecting, staging, and monitoring tumors. Despite their high affinity and specificity, a critical limitation of antibody imaging is the high background signal due to prolonged clearance from the blood, which reduces the tumor-to-background ratio. To address this problem, we developed a molecular imaging probe consisting of multiple self-quenching fluorophores [Cy5.5 or Alexa Fluor 680 (Alexa680)] conjugated to a monoclonal antibody (trastuzumab) to synthesize Tra-Cy5.5(SQ) or Tra-Alexa680(SQ), respectively. This agent only becomes fluorescently active after cellular internalization but is quenched in the unbound state leading to high tumor-to-background ratios. The in vitro quenching capacity for both conjugates was similar to 9-fold. In vivo imaging experiments were done in mice bearing both 3T3/HER-2(+) and BALB/3T3/ZsGreen/HER-2(-) xenografts. Tra-Alexa680(SQ) produced specific enhancement in the 3T3/HER-2(+) tumors but not in the HER-2(-) control tumors. However, Tra-Cy5.5(SQ) produced nonspecific enhancement in both 3T3/HER-2(+) and control tumors. In conclusion, whereas Cy5.5-conjugates produced nonspecific results as well as rapid liver accumulation, conjugating multiple Alexa680 molecules to a single monoclonal antibody resulted in a near-infrared optical agent that activated within specific target tumors with high tumor-to-background ratio with considerable potential for clinical translation. [Mol Cancer Ther 2009;8(1):232-9]
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