Integrating High-Field MRI and CAM-based Experimental Platforms to Accelerate Preclinical Validation of Personalized Lymphoma Therapies

INTERCEPTOR proposes an innovative preclinical platform that integrates high-field Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) with the chorioallantoic membrane (CAM) model to accelerate the validation of precision medicine therapies for B-cell lymphomas, particularly Diffuse Large B-Cell Lymphoma (DLBCL), a malignancy with a high relapse rate following the standard first-line R-CHOP chemoimmunotherapy regimen. To date, no studies have integrated metabolic MRS in CAM tumor models, nor MRI for longitudinal evaluation of drug efficacy in CAM tumor models, and no MRI approaches have been reported to be applied to CAM lymphoma models. Overall, this represents a critical knowledge gap and a unique opportunity for innovation. The novelty of the proposal lies in incorporating advanced structural, functional, and metabolic imaging techniques (T1/T2, DWI/ADC, ¹H/²H MRS) for drug toxicity and efficacy assays within a rapid, ethical, and cost-efficient model, overcoming the limitations of conventional murine-based preclinical workflows. Our starting hypothesis that incorporating MRI into CAM-based lymphoma studies will significantly enhance the predictive power and translational relevance of this preclinical platform will be addressed through four articulated subobjectives: SO1, MRI/MRS protocol optimization; SO2, development of imaging biomarkers for toxicity; SO3, Assessment of the added value of MRI in drug efficacy assays; and SO4, metabolic characterization of DLBCL xenografts. Validation will include four cell line- and four patient-derived xenografts, pre- and post-treatment with standard-of- care R-CHOP and CAR-T therapies. INTERCEPTOR is fully aligned with the Health priority of the Spanish PEICTI 20242027 and Horizon Europe Cluster 1, addressing strategic challenges in oncology through advanced MRI/MRS methodologies applied to lymphoma xenografts. This multidisciplinary approach fosters the development of diagnostic and prognostic tools for precision medicine, advancing knowledge in biomedicine and biotechnology. The team combines complementary expertise in medical physics, preclinical imaging, cancer biology, and molecular biochemistry, supported by a strong track record of Q1 publications, leadership in competitive projects, and collaborations with national and international centers (UAB, CIBER-BBN, Institut Josep Carreras, and i3S in Portugal). Once established, this CAM-MRI methodology can be readily adapted for other tumor types, for testing tailored or targeted treatment strategies, or for in vivo biomaterial testing, expanding its translational impact. Developed protocols will be incorporated as advanced services into the ICTS NANBIOSIS Unit 25 portfolio, enabling broad adoption by academic and industrial partners and promoting technology transfer. Social impact is reinforced by reducing reliance on animal models (3Rs principle) and responding to societal demand for ethical research. Results will be disseminated through open-access publications and presented at leading international conferences (ISMRM, ESMRMB), strengthening visibility and collaborations. Overall, INTERCEPTOR aims to position Spain at the forefront of molecular imaging applied to oncology, delivering innovation, sustainability, and strategic value for translational research.