(TheraGlio-3D) Personalized 3D Tumor models for Precision RadioTheranostics of Glioblastoma

What is TheraGlio-3D about?

During the last decades, new radionuclide-based targeted therapies have emerged as efficient tools for cancer treatment. In particular, since the beginning of the 21st century, the multidisciplinary field of targeted radionuclide therapy (TRT) has been gaining increasing relevance. Based on metabolic or targeted radiopharmaceuticals, TRT allows specific irradiation of localized and disseminated disease with potentially fewer side effects than external beam radiotherapy (EBRT).

This may play an important role in the treatment of the most common and most lethal brain tumor – glioblastoma (GBM) where despite EBRT treatment nearly 100% of patients will experience a local recurrence.  The use of relevant cellular models to investigate the biological effects of ionizing radiation is of crucial importance, namely the molecular and cellular mechanisms involved in the radiation response in GBM.

Leveraging the expertise of the teams in Portugal and at MDACC this exploratory project at the interface of radiation biology and medical physics aims to provide new preclinical insights in radionuclide therapy by evaluating the translational potential of the theranostic radiopharmaceutical 64CuCl2 in advanced patient-derived cell models of GBM, in a precision therapy approach.

What critical challenges is TheraGlio-3D addressing?

Until now most of targeted radionuclide therapy pre-clinical radiobiological studies have been performed in conventional in vitro cell culture systems, which fail to recapitulate some of the features of in vivo tumors. Multicellular tumor spheroids are 3D culture models that can better replicate the metabolic and proliferative gradients of in vivo tumors, and are expected to better contribute to estimate the clinical potential of pharmaceuticals, particularly in a complex environment such as the brain.

How will TheraGlio-3D optimize the Precision radiotheranostics?

The project envisages a strategy for the evaluation of a radiotheranostic approach to GBM based on the use of advanced 3D models. First we will use 3D spheroids, developed in the MD Anderson Cancer Center, and at a later stage explore cerebral organoids that will simulate the microenvironment of a human brain and GBM tumors, allowing a more realistic evaluation of the theranostic potential of 64CuCl2.

How is TheraGlio-3D contributing to medical physics research?

The successful accomplishment of this approach to experimental radiation biology will maximize the translation potential of the theranostic radiopharmaceutical 64CuCl2 in GBM, but also as a therapeutic option for other radiation resistant tumors. Furthermore, the validation of advanced patient-derived 3D models with this simple radiopharmaceutical will also benchmark their future application for the translational evaluation of new target specific radiopharmaceuticals with emergent theranostic pairs of radionuclides which are becoming increasingly relevant for the expansion of cancer therapy. Importantly, this collaborative project will also contribute for the advanced training of young researchers in the strategic areas of medical physics and biomedicine.