24 Sep 2021
Dr. Theodossis Theodossiou describes the potential of protondynamic therapy for treating deep-lying cancers such as glioblastoma multiforme, sharing some preliminary findings reported by his team at the University of Oslo, including how the Oslo Cyclotron Physics Laboratory was equipped to perform this vital biological work. This technology is an exciting new offshoot from photodynamic therapy, which Theodossiou covered in a previous interview with The Scientists’ Channel back in 2019.
Hello, everyone. I am Theodossiou, and I'm a group leader at Oslo University Hospital, Institute for Cancer Research Department of Radiation Biology. This is my second video with Select Science. And, in this video, I would like to present to you some results which are connected with my first video back in 2019. In my previous video, I explained to you the principles of photodynamic therapy and introduced you to a new technology, namely proton dynamic therapy, which is an offshoot of photodynamic therapy conceived and developed in our lab here in Oslo. Photodynamic therapy is a great treatment, but it's limited by light. On the other hand, proton dynamic therapy is based on accelerated protons, exciting the same compounds used in photodynamic therapy. But this time the protons can penetrate up to 25 centimeters in the tissue depending on their initial energy. This can allow us to reach deep line cancers noninvasively in brain or other important organs, which up to now, these cancers have been incurable. The work on proton dynamic therapy was entirely performed at the University of Oslo and, in specific, at the Oslo Cyclotron Lab with the help of our colleagues there. This lab was not equipped for biological work, however, we converted the room into a biolab with the use of an incubator and a hood, which were essential to the work that we did. After preparing the cells in the hood, we radiated them on the Cyclotron beamline with protons, and then put them back into the incubator for further processing. The cells for then taken back to the hospital, and they were analyzed for survival using the MPTSA. Our seminal results from our work on proton dynamic therapy include the production of fluorescence from the radiation of photosensitizer solutions by protons, and the concomitant production of singlet oxygen, which is a main species responsible for cancer cell deaths in photodynamic therapy. Following these promising results, we continued on to cell lines, in particular, glioblastoma multiforme brain tumor cell lines to validate our hypothesis. Indeed, in cell cultures, pre-treated with photosensitizers, we observed 20% to 40% additional deaths than in cell cultures only irradiated by protons. The results presented in this publication are, of course, preliminary. We will move on to animal studies to further validate our hypothesis en vivo. The beauty about proton dynamic therapy is that it can be performed in any of the existing proton therapy centers using their infrastructure with the additional administration of a photosensitizer to the patient. Two of these centers are currently being built here in Norway, one in Oslo, in our campus, and another one in Bergen. We hope to be able to use these centers for the clinical validation of our technology and also to perform the first human trials there. Proton dynamic therapy has the potential of more effective cell-killing than proton therapy itself leading to a curative result. We sincerely hope to be able to treat gruesome ailments like glioblastoma multiforme in one session of proton dynamic therapy, or, in the least, to be able to manage these diseases giving the patient a survival benefit in repeated sessions.
Institute for Cancer Research, Oslo University Hospital
Dr. Theodossis Theodossiou is a senior researcher, and project group leader in the area "Protonics" at the Institue for Cancer Research, Oslo University Hospital. His reasearch group is carrying out research on the use of ionising and non-ionising radiation as cancer therapeutics The main aim of the PROTONICs team is the combinatory use of ionising radiation-based therapies like Proton Therapy and/or Neutron Capture Therapy, together with light based therapies, like Photodynamic Therapy (PDT) or Photochemical Internalisation to achieve a breakthrough anticancer strategy. This multifaceted effort also employs the use of cancer-specific nanoparticles, the use of innovative intracellular light sources for PDT, the interplay between various reactive oxygen species and the use of the cancer cells’ own devices to defeat them. The team further specialises in mitochondrial bioenergetics, the effect of various assaults (chemical, photochemical or radiative) on the mitochondrial respiration and the consequent interplay between respiratory and glycolytic cell metabolism. Our niche is the design and exploration of novel high risk – high gain experimental therapeutics, including not previously envisaged or anticipated strategies. Our activities are currently supported by local (Helse Sor Ost) as well as European funding (Future and Emerging Technologies and Euronanomed).