75P - Pulse mode irradiation regimen of PDT results in high progression free and overall survival in mice with model tumour

Abstract

BackgroundPhotodynamic therapy (PDT) is one of actively developing modalities of cancer treatment. During PDT procedure systemically injected photosensitizer molecules are activated by laser irradiation in tumor location leading to generation of singlet oxygen which induces cytotoxic effect. In modern clinical practice PDT uses continuous wave irradiation. In such mode fast depletion of molecular (triplet) oxygen in tissue occurs leading to reduction of PDT efficiency. Previously we have shown that photodynamic treatment using pulse mode irradiation regimens could be more efficient in damaging tumor cells than standard PDT due to reoxygenation (Klimenko et. al., Photodiagnosis Photodyn Ther., 2016). In present study we have evaluated specially designed pulse mode PDT regimes on tumor model in vivo. MethodsPDT pulse mode irradiation regimens were designed using physics and mathematical modelling. BALB/c male mice were subcutaneous injected into right flanks with CT26 murine colon carcinoma cells. At day ten after inoculation mice were randomized into 3 groups with 10 animals in each (control group, PDT at continuous wave irradiation mode – CW group, PDT at pulse irradiation mode – PM group) and PDT was made. The RadachlorinⓇ photosensitizer and «Lahta-Milon» semiconductor laser (662nm) were used. After treatment the tumor size was estimated every two days. All experiments were performed in accordance with the animal ethics guidelines. ResultsWe have designed new pulse mode irradiation regimens of PDT. We have shown that antitumor efficiency of PDT at pulse irradiation mode is much better than one at standard continuous wave irradiation mode. Median survival after day of treatment was 14 days in control group, 16 days in CW group and 28 days in PM group. In PM group 5 animals had total regress of tumor and progression free survival till the end of experiment (100 days after treatment) compared with only 1 animal in CW group. Thus, we can suggest that overall survival should be much higher in PM group. ConclusionsWe have demonstrated that PDT using pulse mode irradiation regimens is much more effective that PDT using standard regimens and leads to higher progression free and overall survival in mice with CT26 colon carcinoma. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.