Developing novel platforms for delivery and investigation of vascular-targeted photodynamic therapy (VTP) of pre-clinical models of cancer; towards multi-modality prostate cancer therapy.


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Richard Bryant1,Hanna Sjoberg1,Yiannis Philippou1,Iain Tullis1,Danny Allen1,Veerle Kersemans1,Emma Murphy1,Sheena Wallington1,Paul Kinchesh1,Stuart Gilchrist1,Gillies McKenna1,Ian Mills1,Tamar Yechezkel2,Dina Preise2,Lilach Agemy2,Sean Smart1,Boris Vojnovic1,Avigdor Scherz2,Freddie Hamdy1,Ruth Muschel1
1University of Oxford,2The Weizmann Institute of Science

Abstract

Background

Radiotherapy is administered for localised and locally advanced prostate cancer, and provides benefit in low metastatic burden disease. However, it can have significant side-effects, and is not always curative. There is an unmet clinical need to develop multi-modality therapies to improve treatment outcomes for prostate cancer. Vascular-targeted photodynamic therapy (VTP) is a novel safe and effective minimally invasive surgical focal therapy technique for low-risk, low-volume prostate cancer. However, VTP has not been investigated in combination with radiotherapy, or in higher risk disease. It has therefore been necessary to develop a platform to evaluate VTP with ionising radiation in pre-clinical models.

Method

We developed an enclosed optical irradiation system to deliver VTP to flank tumours. A small enclosure contains an animal heating pad, anaesthetic tubing, and connections for physiology monitoring. The enclosure lid contains illumination and fibre-coupled excitation optics, and an XY positioning system to align the output beam to the target area, plus a separate adjustment of beam diameter. A guide beam is provided, and a camera is fitted to simplify laser beam alignment to the target. All system control functions are software controlled. A thermoelectrically-cooled semiconductor laser diode provides VTP excitation, with its output launched into a multimode fibre. Bespoke cradles allow seamless animal transfer from the optical system to a DCE-MRI imaging platform.

Results

Pilot experiments are being performed using a VTP agent activated using 753 nm light. Effects on tumour growth are being evaluated prior to tumour microenvironment evaluation, and combination experiments with ionising irradiation in due course.

Conclusion

We have developed a bespoke enclosed optical irradiation system to deliver VTP to pre-clinical flank tumour cancer models. Experiments are ongoing to establish the efficacy of various VTP treatment conditions, and these results will inform the delivery of multi-modality treatment combining VTP and radiotherapy.