Person:

Hamblin, Michael

This is the first report of photodynamic therapy (PDT) in an orthotopic prostate tumor model and shows that PDT combined with surgery (tumor bed sterilization) gave significant local control of the primary tumor and significant reduction in distant metastases. By contrast, either treatment alone (surgery or PDT) gave relatively poorer local control, and PDT gave a significant increase in the mean number of lung metastases, The MatLyLu variant of the Dunning 3327 rat prostate cancer cell line, which has been selected to be metastatic to lymph nodes and lungs, was injected into the ventral lobe of the rat prostate. After 7 days, tumors were either treated by surgical removal of the ventral lobe, PDT with liposomal benzoporphyrin derivative monoacid ring A, or a combination of surgery, followed by PDT of the tumor bed. Results after 21 days showed a reduction in prostate tumor weight in all groups compared with controls, which became highly significant only for the combination group (17% of control mean tumor weight; P < 0.001; 7 of 13 clinical complete responses). The combination treatment also led to a reduction in lymph node metastasis and reductions in both the frequency and mean number of lung metastases compared with other treatment groups. The PDT-alone group, however, had a mean number of lung metastases per animal, which was nine times the control group and 34 times the combination group. These findings suggest that a tumor bed sterilization approach may be promising for locally advanced prostate cancer and suggest that factors other than local control may need to be evaluated when considering PDT for primary prostate cancer.

The effect of charge modification of photoimmunoconjugates (PICs) on their biodistribution in a xenograft model of ovarian cancer was investigated. Chlorine(e6) c(e6) was attached site specifically to the F(ab')(2) fragment of the murine monoclonal antibody OC125, directed against human ovarian cancer cells, via poly-l-lysine linkers carrying cationic or anionic charges. Preservation of immunoreactivity was checked by enzyme-linked immunosorbent assay (ELISA). PICs were radiolabelled with I-125 and compared with non-specific rabbit IgG PICs after intraperitoneal (i.p.) injection into nude mice. Samples were taken from normal organs and tumour at 3 h and 24 h. Tumour to normal I-125 ratios showed that the cationic OC125F(ab')(2) PIC had the highest tumour selectivity. Ratios for c(e6) were uniformly higher than for I-125, indicating that c(e6) became separated from I-125. OC125F(ab')(2) gave highest tissue values of I-125, followed by cationic OC125F(ab')(2) PIC; other species were much lower. The amounts of c(e6) delivered per gram of tumour were much higher for cationic OC125F(ab')(2) PIC than for other species. The results indicate that cationic charge stimulates the endocytosis and lysosomal degradation of the OC125F(ab')(2)-pl-c(e6) that has bound to the i.p. tumour. Positively charged PICs may have applications in the i.p. photoimmunotherapy of minimal residual ovarian cancer.