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Towards Improved Cancer Treatment: IAEA and Okayama University to Cooperate in Boron Neutron Capture Therapy R&D

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Image of new boron compounds uptake into glioblastoma cancer cells (green: new boron compounds; red: actin; blue: nucleus). (Photo: Okayama University)

Boron Neutron Capture Therapy (BNCT) is a non-invasive therapeutic technique for treating invasive malignant tumours. It relies on the use of neutrons for the generation of energetic alpha particles to destroy cells within the tumour, but not in the surrounding tissue. Recent breakthroughs in accelerator technologies are enabling wider use of this very targeted technique – and the IAEA and Japan’s Okayama University have now signed an agreement that provides a three-year framework for enhanced cooperation in this area.

Patients undergoing BNCT are given a boron-based reagent, often injected intravenously, which accumulates in cancer cells. When a stable boron isotope (boron-10) of the reagent is hit by a beam of neutrons in the cancer cells, it captures neutrons, which causes a nuclear reaction and creation of energetic helium (alpha particle) and lithium nuclei. The nuclei deposit their energy within the tumour cell, causing damage and cell death. The tumour is targeted by selectively introducing the boron reagent into tumour cells, and not by aiming the beam at the cells, as in other radiation therapies, in which healthy tissue still may get damaged as a result. The high biological effectiveness of this procedure and the precisely targeted cell damage are major advantages of BNCT in clinical therapy.  

The effectiveness of BNCT depends mainly on the boron concentration and its distribution in targeted tumour cells, and one of the main R&D challenges remaining is how to increase this concertation. Significant progress has been made over the last few years in optimizing boron compounds and controlling their accumulation in tumour cells. Recently, the most common boron carrier – boronophenylalanine (BPA) – labelled with fluorine-18 (F-BPA) has been developed and successfully applied for monitoring the pharmacokinetics of BPA with positron emission tomography (PET), which allows obtaining information about the tumour as well as evaluating the boron accumulation in both the tumour and in normal tissue. However, further challenges remain:

“The BPA in use currently contains only one boron-10 isotope per molecule. For BNCT to be more successful in destroying the tumour cells, cell targeting agents containing a higher number of boron-10 isotopes in their structure should be developed,” explained Danas Ridikas, Head of the IAEA Physics Section. “This will be one of the main focus of our R&D cooperation activities with Okayama University.”

    Accelerator-based BNCT system under construction, showing electrostatic proton accelerator (on the left) and beam transport line towards neutron production target (on the right). (Photo: Nagoya University)

    Another reason for the renewed interest in BNCT is a recent technological breakthrough made in compact accelerator-based production of neutrons, which allows the installation of accelerators in hospitals and cancer research centres. Just a decade ago, BNCT typically had to be performed in research reactors capable of offering the required intensity and quality of neutron beams for the irradiation of patients. Having to go to an irradiation facility such as a research rector impacted negatively the public acceptance of this therapy. Thanks to recent developments in accelerator technology and accelerator-based neutron production options, patients can now undergo BNCT in a hospital environment just like in more conventional therapies.

    “Further R&D challenges in BNCT are related to the stable operation of high-power accelerators, proton to neutron conversion target technology and neutron dosimetry,” Ridikas said. “Experts worldwide are working on establishing and operating compact neutron sources based on particle accelerators, which are located in university hospitals or cancer therapy centres. Some of these facilities have already started clinical trials.”

    The IAEA and Okayama University previously worked together on various projects related to BNCT, including organizing workshops and events, publishing review stories and coordinating technical visits to relevant therapy centres.

    “BNCT is a cutting-edge cancer therapy. It is a happy marriage of the modern nuclear physics and up-to-date pharmaceutical cell biology,” said Hirofumi Makino, President of the Okayama University. “However, we should not forget the long history of struggle for developing this difficult medical technology. We, the researchers of Okayama University, would like to cultivate a further step of BNCT technologies together with IAEA.”

    The expected outputs of the cooperation include:

    • Capacity building and human resource development through establishing e-learning courses;
    • Organisation of technical events, including a forthcoming IAEA technical meeting in July, with more than 100 registered participants, to assess the current development and usage of the BNCT technique with emphasis on the use of compact accelerator-based neutron sources. Registration for this virtual event is still possible here;
    • Development of a global database of BNCT facilities for information exchange and sharing of good practices among different stakeholders internationally;
    • Exchange of experience and best practice with emphasis on accelerator and target technologies, neutron instrumentation and dosimetry, preparation and evaluation of boron-containing compounds and pharmacological aspects of BNCT; and
    • Preparation and release of an IAEA publication Current status of neutron capture therapy, including updates relevant to progress made in BNCT using compact accelerator driven neutron sources.

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