Periodic Reporting for period 1 - RESPONSE (Early detection of treatment response in breast cancer)
Période du rapport: 2024-06-01 au 2025-09-30
Breast cancer is the most prominent cancer among women globally, with over two million women diagnosed annually. Among men, prostate cancer is the most common with over one million cases every year. Even though early detection and advancements in treatment have led to improved outcomes and survival rates, still, 685,000 women died from breast cancer and 385,000 men died from prostate cancer in 2020. These two cancers, other cancers, cardiometabolic diseases and neurodegenerative diseases require more precise imaging methods to characterize the disease and personalize the treatment. It is thus fundamental to select the best treatment for the individual patient (precision medicine) to improve outcome and reduce side effects (personalized healthcare). However, there are currently no good imaging methods to evaluate the progression of the disease or treatment response in real-time. Patients are treated with radiation therapy, chemotherapy or hormonal therapy and the efficacy of the treatments is only evaluated after several months by assessing if the tumor has reduced in size. With this trial-and-error approach, patients can be subjected to treatments that have no or very little effect, and the patient suffers from the side effects. Importantly, precious time can be lost in finding the right treatment. This has severe consequences for the individual patient. Also, the economic and societal impact is huge as considerable resources are spent on non-effective, expensive treatments, e.g. cancer immunotherapy, in general, is very expensive and can easily cost more than €100,000 per patient with overall success rates of 15-20%. Hyperpolarized Magnetic Resonance (HypMR) is a novel imaging technique that allows radiologists to see inside the body in real-time and with greater detail than ever before. It provides new insights into the function and metabolism of tissues and organs, enabling earlier detection and more accurate diagnosis of diseases such as cancer, heart disease, and neurological disorders. These properties facilitate the development of new treatments and therapies by allowing researchers to track the effects of drugs and other interventions in real-time. The in vivo assessment of tissue metabolism represents a novel strategy for the characterization of cancer and the effectiveness of treatments. This will allow the medical doctor to evaluate, within days to few weeks, whether a treatment effectively kills the cancer cells or not, and to adjust the treatment accordingly. This method is expected to improve selecting the right treatment for the right patient, saving many lives and resources. Society has invested heavily in drug discovery for improved cancer treatment, and overall survival rates are increasing. However, there is still an urgent demand for technologies that are capable of efficiently monitoring the response to treatment of individuals to facilitate actual precision medicine and personalized healthcare, and to reduce costs by supporting fast decisions and beneficial patient management. In this project, we aim to develop a diagnostic imaging test that can measure the response to neoadjuvant treatment for the individual patient in 1-3 weeks instead of the currently more than 12 weeks. Our aim is to develop a diagnostic imaging test for improving treatment decision, by the early detection of response to treatment in breast cancers patients (primary application/use case, although it can be later used across multiple cancer types). Women with advanced breast cancer have reduced five-year survival rate (<75%). However, therapeutic options are vast, and early detection of non-responders will improve patient prognosis and reduce healthcare costs significantly. Our imaging method will enable precision medicine and personalized healthcare for these patients.
- The objective has been to develop and validate clean-in-place manufacture for the preparation of the hyperpolarized contrast agent that is used for HypMR. As part of developing the regulatory strategy we have decided to implement sterile-in-place. The concept has been fully developed and implementation has started: Sterilization by steam (autoclavation) or using the dissolution medium will avoid any chemical cross contamination. Specifically, we have developed a new dissolution module with the capability of producing a full human dose and without any metal parts that could produce metallic leachables. We have also developed a new insertion module that confines the drug (contrast agent) to a controlled environment to minimize the risk that the drug product in the semi-closed process.
- The Quality Control parameters have been decided. It builds on the consensus within the community and a recent consensus article. Only 3-5 optical parameters are measured with a simple spectrophotometer. We developed the principle of how to integrate the QC measurements with the receiver.
- We have initiated a dialogue with Merck to supply the API ([1-13C]pyruvic acid) as individual patient doses. A parallel discussion with a CRO to formulate the API and the processing aid and dispensing into individual patient doses has also been initiated to mitigate the risk that Merck may not want to enter this market yet. The CRO can also supply the dissolution medium and buffer medium.
- We have consulted a CRO (based in Israel) on the regulatory strategy. They have written a report that is the basis of our concept for preparation of the contrast agent. The CRO will guide us in preparing for the dialogue with EMA and national authorities. They will also guide us in building the needed documentation and a Quality Management System.
- 13C coils have been sourced for the Siemens scanner and an open-source pulse sequence platform (Pulseq) has been chosen and implemented on both Siemens and GE scanners. This has allowed us to share pulse sequences between the two sites. UKSH has developed a phantom that is suited for quality assurance in breast imaging.
- The business plan is continuously updated. Dialogue with VC’s is ongoing, but likely the EIC Accelerator path is preferred. The cost of the imaging test will be lower than PET. The key point is superiority to PET in diagnostic value.
- Our Innovation Radar has identified two potential ideas that we may file a patent application on. Both are specific embodiments of the Polarize patent on Clean-In-Place preparation of the hyperpolarized contrast agent.
- We have attended four imaging conferences/symposia to present the hyperpolarization method and the SpinAligner technology. In 2026 and 2027 we have decided what trade conferences to attend to promote the technology.
- The Quality Control parameters have been decided. It builds on the consensus within the community and a recent consensus article. Only 3-5 optical parameters are measured with a simple spectrophotometer. We developed the principle of how to integrate the QC measurements with the receiver.
- We have initiated a dialogue with Merck to supply the API ([1-13C]pyruvic acid) as individual patient doses. A parallel discussion with a CRO to formulate the API and the processing aid and dispensing into individual patient doses has also been initiated to mitigate the risk that Merck may not want to enter this market yet. The CRO can also supply the dissolution medium and buffer medium.
- We have consulted a CRO (based in Israel) on the regulatory strategy. They have written a report that is the basis of our concept for preparation of the contrast agent. The CRO will guide us in preparing for the dialogue with EMA and national authorities. They will also guide us in building the needed documentation and a Quality Management System.
- 13C coils have been sourced for the Siemens scanner and an open-source pulse sequence platform (Pulseq) has been chosen and implemented on both Siemens and GE scanners. This has allowed us to share pulse sequences between the two sites. UKSH has developed a phantom that is suited for quality assurance in breast imaging.
- The business plan is continuously updated. Dialogue with VC’s is ongoing, but likely the EIC Accelerator path is preferred. The cost of the imaging test will be lower than PET. The key point is superiority to PET in diagnostic value.
- Our Innovation Radar has identified two potential ideas that we may file a patent application on. Both are specific embodiments of the Polarize patent on Clean-In-Place preparation of the hyperpolarized contrast agent.
- We have attended four imaging conferences/symposia to present the hyperpolarization method and the SpinAligner technology. In 2026 and 2027 we have decided what trade conferences to attend to promote the technology.
Clean-In-Place and/or Sterile-In-Place preparation of the hyperpolarized contrast agent is beyond state of the art. Our competitors use single-use components that have high costs. We have demonstrated sterility under conditions that are less stringent than the final design. It supports the concept that we are developing this project.
We have implemented imaging methods in Pulseq that can be used across vendor platforms (Siemens and GE Healthcare) for hyperpolarized 13C studies. To our knowledge, there is currently nothing available of this kind. We have validated against the GE Healthcare product tools (Siemens does not have a similar tool) and demonstrated equivalence.
We have implemented imaging methods in Pulseq that can be used across vendor platforms (Siemens and GE Healthcare) for hyperpolarized 13C studies. To our knowledge, there is currently nothing available of this kind. We have validated against the GE Healthcare product tools (Siemens does not have a similar tool) and demonstrated equivalence.