Photodynamic treatment of oral squamous cell carcinoma in hamster cheek pouch model using chlorin p6-histamine conjugate

Summary Background 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. Methods Cp6-his (3 mg/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 4 h after Cp6-his administration were exposed to red light (660 ± 25 nm, 100 J/cm2). 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. Results The accumulation of Cp6-his was higher in tumors as compared to normal mucosa at 4 h 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 48 h from its peak level at 4 h after drug injection. PDT led to extensive cellular damage and tumors of size up to ∼1000 mm3 regressed completely one week after PDT. Conclusion 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.