State-of-the-Art Equipment for Preclinical Targeted Radiotherapy
Lead Research Organisation:
King's College London
Department Name: Imaging & Biomedical Engineering
Abstract
Every two minutes, someone in the UK is diagnosed with cancer and half of cancer patients receive X-ray radiotherapy as part of their therapy. Although advances have been made to better target X-ray radiation beams to where just the tumour is located or use protons beams instead, not all cancer types or stages can be treated with these. Equally, not all tumours respond well to radiotherapy, meaning that it can recur within a few years.
There is therefore still a great need to progress radiation research to 1) not only better predict but also monitor early-on whether radiotherapy is successful, 2) create radioactive injectable therapies that irradiate tumours across the whole body at once, regardless of their size, and 3) test radiotherapy in combination with other drugs that can sensitise tumours (and not healthy tissues) to radiation, thereby decreasing the occurrence of treatment-related side effects.
Here, we will achieve this by purchasing a radiotherapy machine that can accurately target X-ray beams for radiotherapy to tumours in mice and rats in a way that mimics what happens in the clinic. In this way, we can test our well-established (and some novel) injectable radioactive imaging compounds for their ability to monitor how effective new X-ray radiotherapy strategies are in killing tumour cells without damaging healthy tissues. This approach can also be used to predict radiotherapy effectiveness.
Equally, acquiring the animal radiotherapy machine will allow us to create new injectable, radioactive drugs that specifically home to cancer cells anywhere in the body and compare the positives and negatives of this approach to X-ray radiotherapy. Through these studies, we will also understand the relationship between radiation dose delivered and damage to tumour cells as well as healthy cells. This, alongside computer modelling, will inform future clinical trials in terms of required and prescribed injected amounts of radioactive compounds for effective tumour killing at levels that do not damage healthy tissues.
Finally, studies will be carried out to ascertain how effective X-ray radiotherapy and the radioactive compounds are in killing cancer cells that have been pretreated or simultaneously treated with chemo- or other therapies. Hopefully, we will show that combining these therapies with the X-rays or radioactive compounds increases the overall tumour killing ability and work out how this is achieved.
There is therefore still a great need to progress radiation research to 1) not only better predict but also monitor early-on whether radiotherapy is successful, 2) create radioactive injectable therapies that irradiate tumours across the whole body at once, regardless of their size, and 3) test radiotherapy in combination with other drugs that can sensitise tumours (and not healthy tissues) to radiation, thereby decreasing the occurrence of treatment-related side effects.
Here, we will achieve this by purchasing a radiotherapy machine that can accurately target X-ray beams for radiotherapy to tumours in mice and rats in a way that mimics what happens in the clinic. In this way, we can test our well-established (and some novel) injectable radioactive imaging compounds for their ability to monitor how effective new X-ray radiotherapy strategies are in killing tumour cells without damaging healthy tissues. This approach can also be used to predict radiotherapy effectiveness.
Equally, acquiring the animal radiotherapy machine will allow us to create new injectable, radioactive drugs that specifically home to cancer cells anywhere in the body and compare the positives and negatives of this approach to X-ray radiotherapy. Through these studies, we will also understand the relationship between radiation dose delivered and damage to tumour cells as well as healthy cells. This, alongside computer modelling, will inform future clinical trials in terms of required and prescribed injected amounts of radioactive compounds for effective tumour killing at levels that do not damage healthy tissues.
Finally, studies will be carried out to ascertain how effective X-ray radiotherapy and the radioactive compounds are in killing cancer cells that have been pretreated or simultaneously treated with chemo- or other therapies. Hopefully, we will show that combining these therapies with the X-rays or radioactive compounds increases the overall tumour killing ability and work out how this is achieved.
Technical Summary
Despite advances in targeted X-ray radiotherapy to treat cancer, treatment resistance, tumour recurrence, and radiation-induced healthy tissue toxicity are still prevalent and require improvements to be made. Here, we will purchase a preclinical precision X-ray irradiator that delivers conformal X-ray radiation dose to small animals and best mimics clinical image-guided radiotherapy systems. This will enable us to apply our strengths in nuclear medicine, basic science, physics, AI, and clinical translation to radiation research.
Here, radionuclide imaging will be applied to monitor radiotherapy response earlier than currently possible and help visualise underpinning mechanisms of radioresistance. This will guide treatment planning regimens. As well as imaging tumour responses to radiotherapy, we will characterise our panel of imaging tracers to determine whether they can monitor treatment-induced healthy tissue damage early-on.
Acquisition of the preclinical precision irradiator will also help progress our work in molecular radionuclide therapy using alpha particles and Auger electron emitters, more specifically relating their biological effectiveness to radiation absorbed doses, not only for tumours, but also healthy tissues. This will influence the amount of radioactivity that will be administered based on newly defined healthy tissue toxicity limits; the X-ray irradiator will be a key comparator for this work as tissue toxicity limits are currently defined by their sensitivity to X-rays, even when radionuclide therapies are administered.
Finally, studies will be carried out to ascertain whether and how the effectiveness of X-ray and radionuclide therapies can be best enhanced with chemo- or other therapies, such as radiosensitising drugs, hyperthermia, or liposome-encapsulated drugs.
Here, radionuclide imaging will be applied to monitor radiotherapy response earlier than currently possible and help visualise underpinning mechanisms of radioresistance. This will guide treatment planning regimens. As well as imaging tumour responses to radiotherapy, we will characterise our panel of imaging tracers to determine whether they can monitor treatment-induced healthy tissue damage early-on.
Acquisition of the preclinical precision irradiator will also help progress our work in molecular radionuclide therapy using alpha particles and Auger electron emitters, more specifically relating their biological effectiveness to radiation absorbed doses, not only for tumours, but also healthy tissues. This will influence the amount of radioactivity that will be administered based on newly defined healthy tissue toxicity limits; the X-ray irradiator will be a key comparator for this work as tissue toxicity limits are currently defined by their sensitivity to X-rays, even when radionuclide therapies are administered.
Finally, studies will be carried out to ascertain whether and how the effectiveness of X-ray and radionuclide therapies can be best enhanced with chemo- or other therapies, such as radiosensitising drugs, hyperthermia, or liposome-encapsulated drugs.
