Periodic Reporting for period 1 - Thera4Care (THERANOSTICS ECOSYSTEM FOR PERSONALISED CARE)
Periodo di rendicontazione: 2024-10-01 al 2025-09-30
Thera4Care will establish a European Union (EU) network of radiotheranostics centres able to rapidly develop and implement radiotheranostics tools and solutions to drive precision health. The overarching vision of Thera4Care is to revolutionise radiotheranostics procedures by establishing, implementing, and disseminating standardised scalable methods to produce and efficiently administer key radiotheranostics solutions. Thera4Care focuses on developing diagnostic and therapeutic ligands tailored to key disease areas (such as solid tumours), aligning with the growing significance of multi-modal radiotheranostics solutions dominated by radionuclide-based therapy and companion diagnostics. These solutions are emerging as safe, personalised, and effective approaches for treating various diseases. However, the current utilisation of such therapies is limited to a few specialised centres, necessitating an increase in clinical treatment capacities. Additionally, there is a need to broaden the arsenal of radiotheranostics, potentially incorporating novel non-nuclear approaches. In the context of this broader vision, Thera4Care aims to leverage or create standardised and scalable radiochemical methods for labelling, developing, and producing diagnostic and therapeutic ligands. This includes the exploration of new, and innovative combinations of existing multi-modal radiotheranostics, encompassing both radiopharmaceuticals and non-radioactive solutions. The main aim is to address the challenge of limited accessibility to these advanced therapies, especially in the context of diseases with unmet public health needs, such as oncology, neurology, and advanced multi-disease conditions.
To further support Thera4Care’s vision, the consortium intends to establish precise positron emission tomography (PET) and Single-photon emission computed tomography (SPECT) imaging-based diagnostic and therapy monitoring protocols for the identified radiotheranostics ligands. Simultaneously, Thera4Care is committed to developing standardised and scalable dosimetry, quantitation, therapy-selection, and timely supply methodologies to ensure precise treatment and optimise patient outcomes. Furthermore, we envision the creation of an approved clinical trial master protocol designed for evaluating radiotheranostics procedures in hospitalised patients during phase I/IIa trials. This master protocol, developed through a collaborative European effort, will accelerate the time to treat patients with promising radiotheranostics procedures.
In this pursuit of innovation, Thera4Care is dedicated to preclinically exploring various compound/radionuclide combinations in cancer indications with unmet medical needs, such as solid tumours. Subsequently, clinical proof-of-concept evaluations will be performed for the most promising radiotheranostics solutions identified through the master protocol's development. The comprehensive approach of the project aims to propel the field of radiotheranostics, addressing critical medical challenges and improving patient care.
To further support Thera4Care’s vision, the consortium intends to establish precise positron emission tomography (PET) and Single-photon emission computed tomography (SPECT) imaging-based diagnostic and therapy monitoring protocols for the identified radiotheranostics ligands. Simultaneously, Thera4Care is committed to developing standardised and scalable dosimetry, quantitation, therapy-selection, and timely supply methodologies to ensure precise treatment and optimise patient outcomes. Furthermore, we envision the creation of an approved clinical trial master protocol designed for evaluating radiotheranostics procedures in hospitalised patients during phase I/IIa trials. This master protocol, developed through a collaborative European effort, will accelerate the time to treat patients with promising radiotheranostics procedures.
In this pursuit of innovation, Thera4Care is dedicated to preclinically exploring various compound/radionuclide combinations in cancer indications with unmet medical needs, such as solid tumours. Subsequently, clinical proof-of-concept evaluations will be performed for the most promising radiotheranostics solutions identified through the master protocol's development. The comprehensive approach of the project aims to propel the field of radiotheranostics, addressing critical medical challenges and improving patient care.
Objective 1 – Develop an Integrated Radiotheranostic Pipeline with new radiotheranostic solutions and plan an early phase clinical trial to compare conventional to innovative radiotheranostic pathways in healthcare.
The development and submission of the prospective phase I/II clinical trial package has begun, employing the Clinical Trials Information System (CTIS) including CMC for the 161Tb FAPI trial in FAP expressing metastatic solid tumours. The clinical trial package includes the investigative brochure (IB), the investigational medicinal product dossier, an IRB-protocol as well as the required radiation safety material.
Objective 2 – Develop a digital platform to streamline cancer care by implementing Artificial Intelligence (AI)-based tools for the quantification of disease burden through multimodal data integration (multimodal imaging, AI and pathology models).
The coordination, governance, and technical foundations for the development of the Multisite Multimodal FAIR Data-Sharing Platform has been established. Initial discussions on tumour-segmentation guidelines were initiated to promote methodological alignment across modalities and sites, ensuring future AI models can be trained and validated on harmonised, high-quality datasets. REDCap data-dictionary samples were collected to inform upcoming data-normalisation and metadata-harmonisation activities.
Objective 3. Improvement and broadening of the European radiotheranostic manufacturing capabilities and treatment capacities, including standardisation, knowledge, quality, production, supply and departmental organisation.
Preclinical investigations of ¹⁶¹Tb-based FAPI radiopharmaceuticals have been conducted. In parallel, 44Sc was preliminarily suited for PET imaging and regarded as the corresponding diagnostic pair. While the separation method is being optimised further, activity was provided for 44Sc-FAPI labelling experiments. Plans are ongoing to establish production of ⁶⁴Cu-FAPI-74 for WP3 supply. In addition, feasibility studies are ongoing to test the feasibility of using 67Cu for preclinical studies, considering the production yield, half-life and shipment time. The design of uPAR-targeting molecules compatible with 211At labelling has been completed, and the synthesis of these compounds is currently in progress. The next step is to test and optimise labelling with 211At and test stability of the compounds ahead of supplying WP3.
Objective 4 – Education and training on radiotheranostic solutions and integration in clinical settings, underlining the role of multidisciplinary teams, multimodality imaging and personalised novel therapies.
A Plan for Communication and Dissemination has been established, Project website (www.thera4care.eu) was set up for project communication, social media outreach on LinkedIn gained 1000 followers as of August 2025.
Thera4Care was showcased on the international stage at the EANM25 Congress, which involved a live discussion about the project with attendees and Template documents (presentation, poster, deliverable) are now ready for consortium use. Moreover 2 Annual Meetings were organised in different sites with official consortium partners (October 2024 in Rome, May 2025 in Budapest). Thanks to the collaboration between WP1 and WP9, weekly and monthly coordination meetings have been promoted in the Core Group (WP1) and all single WPs Leaders (WP2 to WP9), to ensure timely communication and coordination among WP and Task Leaders.
The development and submission of the prospective phase I/II clinical trial package has begun, employing the Clinical Trials Information System (CTIS) including CMC for the 161Tb FAPI trial in FAP expressing metastatic solid tumours. The clinical trial package includes the investigative brochure (IB), the investigational medicinal product dossier, an IRB-protocol as well as the required radiation safety material.
Objective 2 – Develop a digital platform to streamline cancer care by implementing Artificial Intelligence (AI)-based tools for the quantification of disease burden through multimodal data integration (multimodal imaging, AI and pathology models).
The coordination, governance, and technical foundations for the development of the Multisite Multimodal FAIR Data-Sharing Platform has been established. Initial discussions on tumour-segmentation guidelines were initiated to promote methodological alignment across modalities and sites, ensuring future AI models can be trained and validated on harmonised, high-quality datasets. REDCap data-dictionary samples were collected to inform upcoming data-normalisation and metadata-harmonisation activities.
Objective 3. Improvement and broadening of the European radiotheranostic manufacturing capabilities and treatment capacities, including standardisation, knowledge, quality, production, supply and departmental organisation.
Preclinical investigations of ¹⁶¹Tb-based FAPI radiopharmaceuticals have been conducted. In parallel, 44Sc was preliminarily suited for PET imaging and regarded as the corresponding diagnostic pair. While the separation method is being optimised further, activity was provided for 44Sc-FAPI labelling experiments. Plans are ongoing to establish production of ⁶⁴Cu-FAPI-74 for WP3 supply. In addition, feasibility studies are ongoing to test the feasibility of using 67Cu for preclinical studies, considering the production yield, half-life and shipment time. The design of uPAR-targeting molecules compatible with 211At labelling has been completed, and the synthesis of these compounds is currently in progress. The next step is to test and optimise labelling with 211At and test stability of the compounds ahead of supplying WP3.
Objective 4 – Education and training on radiotheranostic solutions and integration in clinical settings, underlining the role of multidisciplinary teams, multimodality imaging and personalised novel therapies.
A Plan for Communication and Dissemination has been established, Project website (www.thera4care.eu) was set up for project communication, social media outreach on LinkedIn gained 1000 followers as of August 2025.
Thera4Care was showcased on the international stage at the EANM25 Congress, which involved a live discussion about the project with attendees and Template documents (presentation, poster, deliverable) are now ready for consortium use. Moreover 2 Annual Meetings were organised in different sites with official consortium partners (October 2024 in Rome, May 2025 in Budapest). Thanks to the collaboration between WP1 and WP9, weekly and monthly coordination meetings have been promoted in the Core Group (WP1) and all single WPs Leaders (WP2 to WP9), to ensure timely communication and coordination among WP and Task Leaders.
In the first year of the project, the following points have been fixed for further evaluation.
- Improving availability of effective treatments: Novel radionuclide-targeted therapies, Identification of synergistic combinations of radioligands with immune-, chemotherapeutic, and targeted drugs.
- Stronger resilience for Europe’s health systems: Establishment of standardised trusted GMP production sites, production methods and networks, Increasing diagnostic accuracy through precision imaging.
- Contributing to Europe’s Beating Cancer plan and Cancer Mission: Improving diagnostic accuracy through precision imaging, Improving therapeutic efficacy, Optimising treatment (therapeutic regimens and dosimetry), Improving early detection
- Improving availability of effective treatments: Novel radionuclide-targeted therapies, Identification of synergistic combinations of radioligands with immune-, chemotherapeutic, and targeted drugs.
- Stronger resilience for Europe’s health systems: Establishment of standardised trusted GMP production sites, production methods and networks, Increasing diagnostic accuracy through precision imaging.
- Contributing to Europe’s Beating Cancer plan and Cancer Mission: Improving diagnostic accuracy through precision imaging, Improving therapeutic efficacy, Optimising treatment (therapeutic regimens and dosimetry), Improving early detection