chlorin-p6 and Disease-Models--Animal

Over-expression of histamine receptors has been reported in several types of malignancies. Earlier we have successfully demonstrated use of chlorin p6-histamine conjugate (Cp6-his) for improving cellular uptake and photo toxicity of Cp6 in oral cancer cell lines. In the present study, after having confirmed that histamine receptors are over-expressed in tumors of hamster cheek pouch, we investigated the efficacy of Cp6-his for photodynamic treatment (PDT) of tumors in this animal model.. Cp6-his (3mg/kg body weight) was injected intraperitoneally and its accumulation in tumor, surrounding tissue, normal mucosa and abdominal skin was monitored non-invasively by fluorescence spectroscopy. For PDT, tumors at 4h after Cp6-his administration were exposed to red light (660±25nm, 100J/cm(2)). Tumor damage and regression were assessed by histology and tumor volume measurements, respectively. Expression of histamine H2 receptors in tumor and normal mucosa was assessed by immuno-staining.. The accumulation of Cp6-his was higher in tumors as compared to normal mucosa at 4h after its administration. For Cp6 similar preferential accumulation was observed except that in normal mucosa the accumulation of Cp6 was more as compared to Cp6-his. The clearance of Cp6-his from skin was rapid showing ∼80% decrease within 48h from its peak level at 4h after drug injection. PDT led to extensive cellular damage and tumors of size up to ∼1000mm(3) regressed completely one week after PDT.. Higher tumor selectivity of Cp6-his and complete regression of bigger tumors after PDT suggest that conjugating Cp6 to histamine is a promising approach to improve PDT efficacy.

Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cheek; Cricetinae; Disease Models, Animal; Histamine; Humans; Male; Mesocricetus; Mouth Neoplasms; Photosensitizing Agents; Porphyrins; Treatment Outcome