In Vivo Quantification of Tumor Receptor Binding Potential with Dual-Reporter Molecular Imaging
- 594 Downloads
Receptor availability represents a key component of current cancer management. However, no approaches have been adopted to do this clinically, and the current standard of care is invasive tissue biopsy. A dual-reporter methodology capable of quantifying available receptor binding potential of tumors in vivo within a clinically relevant time scale is presented.
To test the methodology, a fluorescence imaging-based adaptation was validated against ex vivo and in vitro measures of epidermal growth factor receptor (EGFR) binding potential in four tumor lines in mice, each line expected to express a different level of EGFR.
A strong correlation was observed between in vivo and ex vivo measures of binding potential for all tumor lines (r = 0.99, p < 0.01, slope = 1.80 ± 0.48, and intercept = −0.58 ± 0.84) and between in vivo and in vitro for the three lines expressing the least amount of EGFR (r = 0.99, p < 0.01, slope = 0.64 ± 0.32, and intercept = 0.47 ± 0.51).
By providing a fast and robust measure of receptor density in tumors, the presented methodology has powerful implications for improving choices in cancer intervention, evaluation, and monitoring, and can be scaled to the clinic with an imaging modality like SPECT.
Key wordsMolecular imaging Fluorescence Targeted reporter Epidermal growth factor receptor Mouse model
- 15.Samkoe KS, Sexton K, Tichauer KM, et al. (2011) High vascular delivery of EGF, but low receptor binding rate is observed in AsPC-1 tumors as compared to normal pancreas. Mol Imaging Biol. doi:10.1007/s11307-011-5203-5
- 24.McLarty K, Cornelissen B, Scollard DA, Done SJ, Chun K, Reilly RM (2009) Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts. Eur J Nucl Med Mol Imaging 36:81–93PubMedCrossRefGoogle Scholar
- 28.Franceschini MA, Gratton E, Hueber D, Fantini S (1999) Near-infrared absorption and scattering spectra of tissues in vivo. In Proceedings of SPIEGoogle Scholar