Discrimination between normal and premalignant tissues by fluorescence imaging and/or spectroscopy may be enhanced by a
tumor-localizing fluorescent
drug. Ethyl
Nile Blue A (
EtNBA), a
dye with no phototoxic activity, was investigated for this purpose. The pharmacokinetics and tissue-localizing properties were investigated in a rat palate model with chemically induced premalignant mucosal lesions (0.5 mg/kg
EtNBA intravenous [i.v.]), a hairless mouse model with UVB-induced premalignant skin lesions (1 mg/kg
EtNBA intraperitoneal) and in a rat skin-fold observation chamber model on the back of a rat with a transplanted solid
tumor (2.5 mg/kg
EtNBA i.v.). Fluorescence images and spectra were recorded in vivo (600 nm excitation, 665-900 nm detection) and in frozen tissue sections at several time points after
EtNBA administration. In the rat palate the
EtNBA fluorescence was maximum almost immediately after injection, whereas in the mouse skin and the observation chamber the fluorescence maximum was reached between 2 and 3 h after injection.
EtNBA cleared from tissues after 8-24 h.
EtNBA localizes in the transplantable solid
tumor, but is not targeted specifically to the dysplastic location in the rat palate and mouse skin. However, in the rat palate the
EtNBA fluorescence increased significantly with increasing dysplasia, apparently due to the increasing thickness of the upper keratinized layer of the epithelium where the
dye was found to localize. Localization in this layer occurred both in the rat palate and in hairless mouse skin.