At a glance
|Title||Theranostic Strategy for Proton Boron Capture Therapy of Pancreatic Cancer|
|Scientific Area||Medical Physics for Emerging Cancer Therapies|
|Funding (PT)||49 634,8 EUR|
|Funding (US)||50 002 USD|
|Leading Institutions||Associação do Instituto Superior Técnico para a Investigação e o Desenvolvimento (IST-ID), PT
Department of Cancer Systems Imaging, MD Anderson Cancer Center, The University of Texas, USA
|Duration||12 months 15 months|
|Start date||April 1, 2022|
|End date||March 31, 2023 June 30, 2023|
|Keywords||Proton Therapy, Nanomedicine, Proton-Boron Fusion Reaction, Radiobiological Effects|
What is THER-PBCT about?
Pancreatic cancer is the seventh leading cause of cancer deaths in industrialized countries, according to the Global Cancer Statistics of 2018.
This project will study the delivery of boronated micelles to radioresistant pancreatic cancer cells and will evaluate their biological responses upon irradiation with an 80-MeV clinical proton beam at the MD Anderson Cancer Center (MDACC) facilities.
We expect to demonstrate that the Proton Boron Capture Therapy (PBCT) approach will lead to a significant dose enhancement factor, fostering the PBCT usefulness for the treatment of pancreatic carcinoma. For this purpose, we will use polymeric micelles that will encapsulate boronated rhenium complexes for an augmented delivery of boron atoms to pancreatic tumour cells.
What critical challenges is THER-PBCT addressing?
Proton beams correspond to low LET (Linear Energy Transfer) radiation with relative biological effectiveness (RBE) usually considered to be only ten per cent larger than the RBE of gamma or X-ray radiation, which limits its usefulness in the treatment of radioresistant tumours, like pancreatic carcinoma. Thus, the enhancement of the efficacy of proton therapy has been pursued through different strategies, such as the combination with other anticancer modalities (e.g., immunotherapy or chemotherapy) or by employing radiosensitizing agents. As proposed in this project, one possible alternative to enhance the RBE in proton therapy is the so-called PBCT approach that relies on a reaction that occurs in vivo in the tumours to be eradicated.
How will PBCT be tested as a treatment for pancreatic carcinoma?
Initially, cytotoxicity studies and cellular uptake studies will be performed to select the best performing system for the proton irradiation studies at MDACC, (i.e. the one showing the highest cellular boron uptake and lowest cytotoxicity). To provide the proposed PBCT strategy with a theranostic nature, the boronated micelles will be labelled with Technetium-99m (Tc-99m) complexes to allow the Single Photon Emission Computed Tomography (SPECT) imaging of the micelles accumulation in the tumours of pancreatic carcinoma mice models.
How is THER-PBCT likely to impact cancer treatment?
Pancreatic cancer will become the second leading cause of tumour-related mortality in the next decade, according to the current estimations. Hence, more efficacious treatments are urgently needed to treat this radioresistant tumour, known as one of the “big killers”. Towards this goal, we expect that this project will unravel the potential of PBCT as an innovative approach to improve the efficacy of proton therapy in the treatment of radioresistant tumours, such as pancreatic carcinoma. If successful, our strategy will contribute to more personalized radiotherapy of pancreatic cancer, together with a better ability to predict the therapeutic outcome.
Key Expected Outcomes
- Positive impact on the Portuguese research team, as C2TN/IST researchers will be acquainted with skills and knowledge, which will allow them to participate in preclinical proton therapy studies at the Proton Therapy facility planned to be installed in Portugal, at the Campus Tecnológico e Nuclear (CTN) campus;
- Publication of 1 paper in an international journal;
- Presentation of 2-3 communications in international conferences.
Papers and Communications
- Nuez-Martínez, M., Queralt-Martín, M., Muñoz-Juan, A., Aguilella, V. M., Laromaine, A., Teixidor, F., Viñas, C., Pinto, C. G., Pinheiro, T., Guerreiro, J. F., Mendes, F., Roma-Rodrigues, C., Baptista, P. V., Fernandes, A. R., Valic, S., & Marques, F. (2022). Boron clusters (ferrabisdicarbollides) shaping the future as radiosensitizers for multimodal (chemo/radio/PBFR) therapy of glioblastoma. In Journal of Materials Chemistry B (Vol. 10, Issue 47, pp. 9794–9815). Royal Society of Chemistry (RSC).
- Other team members in Portugal: Célia Fernandes (co-PI; C2TN/IST), Fernanda Marques (C2TN/IST), Filipa Mendes (C2TN/IST), Francisco Silva (C2TN/IST), Lurdes Gano (C2TN/IST)
- Other team members in Austin: Joe Y.Chan (MDACC/UT Austin), Qizhen Cao (MDACC/UT Austin)