Photochemical internalization (PCI) of bleomycin is equally effective in two dissimilar leiomyosarcoma xenografts in athymic mice

BackgroundPhotochemical internalization (PCI) is a novel technique for delivery of active macromolecules into cancerous cells, via light activation of a specific photosensitizer and a low dose systemic drug. Numerous pre-clinical studies and one clinical trial have confirmed the treatment potential in carcinomas. Soft tissue sarcomas are rare and generally resistant to radio- and chemotherapy. Due to treatment resistance and surgical morbidity in sarcoma care, we seek to increase knowledge on PCI effects in sarcomas by studying two different, but closely related leiomyosarcomas.MethodsMES-SA and SK-LMS-1 tumours were established in the leg muscles of athymic mice. Treatment effects after AlPcS_2a-PCI of bleomycin, PCI with no drug (photodynamic therapy, PDT) and control groups were evaluated by: 1) assessment of tumour growth, 2) uptake of contrast agent during MRI and 3) histopathology.ResultsPCI of bleomycin induced a similar and significant increase in time to reach the end point in both tumour models, while neither responded to AlPcS_2a-PDT. In the MES-SA tumours PCI reduced the growth rate, while in the SK-LMS-1 tumours the growth was blocked for 12 days followed by exponential growth close to that of untreated tumours. SK-LMS-1 tumours were more homogenously and better vascularized than MES-SA. After PCI the vascular shutdown was more complete in the SK-LMS-1 tumours than in the MES-SA tumours.ConclusionsAlPcS2a-based PCI, but not PDT, induced significant tumour growth delay in the evaluated sarcomas. Cellular responsiveness to bleomycin and tumour vascularity are identified as predictive markers for PCI treatment effects.