Periodic Reporting for period 1 - ILLUMINATE (INCREASING LUTETIUM PRODUCTION, WHILE LEVERAGING METABOLIC IMAGING TO ENHANCE THERANOSTICS EFFECTIVENESS)
Reporting period: 2024-10-01 to 2025-09-30
Patients with advanced metastatic prostate cancer (AMPC) can be treated with Lutetium (Lu)-177-PSMA, which extends their survival by several months. However, some patients benefit more than others, and some only suffer from side effects. Currently, we cannot tell upfront nor during treatment who will benefit.
Moreover, the treatment itself is at risk of insufficient supply due to its popularity and sensitivities in its manufacturing line.
ILLUMINATE is set up to improve availability and use of theranostics across the complete value chain. It aims to:
Develop innovative theranostic solutions by updating Metabolic MRI (MeMRI) components and technologies for application as Clinical Investigational Device (WP1). These will be validated in an observational clinical trial with Lu-177-PSMA in patients with AMPC to demonstrate the added value of MeMRI (WP3).
This new imaging biomarker aims acts as an additional triage tool. The biomarker will be designed via the use of 31P and 2H magnetic resonance spectroscopic imaging, which will provide metabolic images (MeMRI) that reflect cell proliferation and inefficient energy metabolism. The most sensitive MRI systems (7T) will be updated so that they can optimally detect metabolites in the human body. A scan protocol will be realized that it is tolerable for patients, and tested in a clinical trial (WP3).
Develop quantification & decision-making models, and broadly applicable MeMRI decision making tools (WP1). This will aid in a) personalizing the treatment and disease management of patients, and b) reducing the required supply of radioisotopes based on improved patient stratification, dosing, and cessation of treatment.
Broaden the availability of MeMRI technology by facilitating its application across different platforms (WP2). Easier to scale MeMRI technology will be prepared and made available to the wider clinical society (for widely available clinical 1.5T MRI) by making use of a technology called chemical exchange by saturation transfer (CEST). This technology requires a contrast agent and subtle upgrades to 1.5T MRI systems.
Improve manufacturing capability by increasing capacity of Lu-177 production, development of a recycling process for the starting material Ytterbium, and by developing expertise on centralized preparation of Lu-177 radiopharmaceuticals (WP2). This approach aims to make the supply chain of Lu-177 more robust and make Lu-177 more widely available in the EU.
Investigate and develop relevant rules, regulations and policies to improve access to the developed technologies (WP4). A guideline for in-house manufacturing of metabolic profiling on a 7T MR scanner will be developed. A regulatory strategy will be developed for radionuclide-based theranostics. We also aim to investigate Lu treatment policies in different EU countries. This can inform policy making, and might provide new opportunities to reduce healthcare costs, increase patient satisfaction, and make the treatment wider available.
Ensure stakeholder engagement by developing and executing a patient engagement plan and by establishing a stakeholder involvement community (STIC),, and collect health care professional experiences, increasing chances for sustainable outcome implementation of outcome and follow-up beyond the project (WP5).
Develop training materials for (medical) professionals based on the developed solutions, and disseminate these through workshops, conferences and training and integration into educational programmes (WP5).
Communicate and disseminate the results and overall progress to a wide audience. Provide excellent project & partnership management to steer the consortium towards success.
Moreover, the treatment itself is at risk of insufficient supply due to its popularity and sensitivities in its manufacturing line.
ILLUMINATE is set up to improve availability and use of theranostics across the complete value chain. It aims to:
Develop innovative theranostic solutions by updating Metabolic MRI (MeMRI) components and technologies for application as Clinical Investigational Device (WP1). These will be validated in an observational clinical trial with Lu-177-PSMA in patients with AMPC to demonstrate the added value of MeMRI (WP3).
This new imaging biomarker aims acts as an additional triage tool. The biomarker will be designed via the use of 31P and 2H magnetic resonance spectroscopic imaging, which will provide metabolic images (MeMRI) that reflect cell proliferation and inefficient energy metabolism. The most sensitive MRI systems (7T) will be updated so that they can optimally detect metabolites in the human body. A scan protocol will be realized that it is tolerable for patients, and tested in a clinical trial (WP3).
Develop quantification & decision-making models, and broadly applicable MeMRI decision making tools (WP1). This will aid in a) personalizing the treatment and disease management of patients, and b) reducing the required supply of radioisotopes based on improved patient stratification, dosing, and cessation of treatment.
Broaden the availability of MeMRI technology by facilitating its application across different platforms (WP2). Easier to scale MeMRI technology will be prepared and made available to the wider clinical society (for widely available clinical 1.5T MRI) by making use of a technology called chemical exchange by saturation transfer (CEST). This technology requires a contrast agent and subtle upgrades to 1.5T MRI systems.
Improve manufacturing capability by increasing capacity of Lu-177 production, development of a recycling process for the starting material Ytterbium, and by developing expertise on centralized preparation of Lu-177 radiopharmaceuticals (WP2). This approach aims to make the supply chain of Lu-177 more robust and make Lu-177 more widely available in the EU.
Investigate and develop relevant rules, regulations and policies to improve access to the developed technologies (WP4). A guideline for in-house manufacturing of metabolic profiling on a 7T MR scanner will be developed. A regulatory strategy will be developed for radionuclide-based theranostics. We also aim to investigate Lu treatment policies in different EU countries. This can inform policy making, and might provide new opportunities to reduce healthcare costs, increase patient satisfaction, and make the treatment wider available.
Ensure stakeholder engagement by developing and executing a patient engagement plan and by establishing a stakeholder involvement community (STIC),, and collect health care professional experiences, increasing chances for sustainable outcome implementation of outcome and follow-up beyond the project (WP5).
Develop training materials for (medical) professionals based on the developed solutions, and disseminate these through workshops, conferences and training and integration into educational programmes (WP5).
Communicate and disseminate the results and overall progress to a wide audience. Provide excellent project & partnership management to steer the consortium towards success.
The meMRI is successfully operational for the sites that provide ~67% of the patients for the clinical trial. The technology for the site in Essen requires a software patch that has been purchased, deployed, and tested (in accordance with the original plan). 2 scientific abstracts have been submitted/presented on the preliminary results from healthy participants.
upscaling to sites is ongoing for both the 7T as well as the CEST. The designs are completed, and the installations are scheduled.
data processing for the meMRI is agreed upon and implemented in a user-friendly matlab program. Fine tuning of data reconstruction is under investigation and may be implemented prior to starting the trial.
clinical trial protocol is under development. Start of the trial is expected in Q1 2026
Active members were enrolled to the STIC and present at consortium meeting. The STIC have reviewed the draft of the information brochure and provided feedback to researchers in several F2F sessions.
preparation for upscaling the meMRI to contrast enhanced CEST is demonstrated in completed preclinical studies; a clinical pilot scan is being prepared.
first attempt for upscaling for Lu177 did not show sufficient separation of starting material. The second mechanism for upscaling is being prepared.
relevant governance and internal communication structures have been set up. A F2F kick-off meeting was organized. A F2F annual meeting was organized to update each other on progress and openly obtain advice from STIC and SAB. A Legal Team was established, the initial Sustainability Plan and and the Initial Data Management Plan were developed.
A communication and dissemination strategy was set up, and the execution of this strategy has started.
upscaling to sites is ongoing for both the 7T as well as the CEST. The designs are completed, and the installations are scheduled.
data processing for the meMRI is agreed upon and implemented in a user-friendly matlab program. Fine tuning of data reconstruction is under investigation and may be implemented prior to starting the trial.
clinical trial protocol is under development. Start of the trial is expected in Q1 2026
Active members were enrolled to the STIC and present at consortium meeting. The STIC have reviewed the draft of the information brochure and provided feedback to researchers in several F2F sessions.
preparation for upscaling the meMRI to contrast enhanced CEST is demonstrated in completed preclinical studies; a clinical pilot scan is being prepared.
first attempt for upscaling for Lu177 did not show sufficient separation of starting material. The second mechanism for upscaling is being prepared.
relevant governance and internal communication structures have been set up. A F2F kick-off meeting was organized. A F2F annual meeting was organized to update each other on progress and openly obtain advice from STIC and SAB. A Legal Team was established, the initial Sustainability Plan and and the Initial Data Management Plan were developed.
A communication and dissemination strategy was set up, and the execution of this strategy has started.
Interleaved or simultaneous scanning of 31P as well as 2H metabolic MRI is shown feasible, which relaxes the scan time for the patient. However, standard scanner software is not capable of providing this feature, so industries require extra investment to incorporate this into their product. For now, the clinical trial will not include this interleaved scanning option.
Reconstruction can be improved to avoid signal intensity bias using a novel technique of multiple frequency normalizations (feasible in both 31P and 2H). This technique can be embedded in the matlab routine.
CEST can be transferred to 31P as well, providing novel contrast mechanisms never experienced before. We will seek further funding to investigate this novel biomarker in the near future but will not make this part of the clinical trial.
Reconstruction can be improved to avoid signal intensity bias using a novel technique of multiple frequency normalizations (feasible in both 31P and 2H). This technique can be embedded in the matlab routine.
CEST can be transferred to 31P as well, providing novel contrast mechanisms never experienced before. We will seek further funding to investigate this novel biomarker in the near future but will not make this part of the clinical trial.