In vivo characterization of tissue efflux rates of cyanine dyes by near-infrared spectroscopy

Optical mammography is a new imaging modality currently under development. A contrast agent capable of adding malignancy differentiation signatures is expected to enhance the sensitivity and specificity characteristics of the technique. We report the in vivo characterization of hydrophilic analogs of indocyanine green (ICG) that lead to enhanced tumor absorbance compared to surrounding tissue. The tumor efflux of these dyes was quantitatively studied in tumor-bearing rats by frequency-modulated near-infrared spectroscopy. We demonstrate that the half-lifes of hydrophilic cyanine dyes in tumor tissue are considerably enhanced compared to ICG, thus providing a prolonged time window for diagnosis. Moreover, absorption differences between the tumor and normal tissue were observed for 3 hours after injection of the hydrophilic glucamine derivative NIR96010. In conclusion, pharmacokinetic properties as present with NIR96010 may facilitate contrast-agent-aided optical mammography.