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Geant4-DNAを用いた水放射線分解生成種の定量評価

馬場, 健太郎 北海道大学

2022.03.24

概要

放射線がん治療は生活の質(QOL)を維持しながら治療を行えるという利点から大きな注目を浴びている。特に、陽子線や炭素イオン線などの粒子線がもつ放射線生物学的特徴はがん治療に適しており、十分な臨床試験を経て実用化され、外科療法に勝るとも劣らない実績を上げている。これは粒子線が特異な照射効果を有するためであり、例えば粒子線の生物学的効果比(RBE)が高いことや、酸素増感比(OER)が小さいことが挙げられる。こうした特異性は現象論的によく調べられており実際の治療計画でも考慮されているものの、生じる詳細なメカニズムは未だよく分っていない。近年では、粒子線のもつ特異性を説明するには生体主成分の水が粒子線によりどう分解されるかが重要であるとされている。

そこで、信頼性の高い放射線治療を実現するには水の放射線分解生成種が粒子線治療の生物学的影響・治療効果においてどのような役割を果たすのか解明する必要があると考え、オープンソースのモンテカルロシミュレーションツールキット「Geant4-DNA」を用いて放射線分解により生じる化学種(ラジカルなど)の化学反応過程を計算することで、粒子線照射下における水の放射線分解生成種の定量評価に取り組んだ。

第1章では、粒子線ブラッグピーク周辺のエネルギー領域におけるOHラジカル収量(G値)の定量評価を試みた。周囲と比べて格段に高いエネルギー付与密度が期待できるブラッグピーク周辺では、イオントラックに沿って高密度に放射線分解生成種が生成されるため、ラジカル同士の反応をより正確にシミュレートしなければ実験値を再現する結果を得ることはできない。本研究では、Geant4-DNA version 10.05.p01には未実装であった化学種(O•-,O2,O2•-,HO2•,HO2-)とこれらが関与する化学反応を新たに計算に追加することによって、これまでシミュレーション計算で再現することが困難であった重イオン線ブラッグピーク周辺のエネルギー領域におけるOHラジカルのG値の実験値を再現することに成功した。しかし、典型的な水の放射線分解生成種であるOHラジカル、水和電子に関しては1eV/nmから700eV/nmの広いLET範囲で実験値を再現することができたが、H2O2のG値に関してLETが200eV/nmを超える領域にてシミュレーションの計算結果は実測結果と異なる傾向を示した。この不一致はGeant4-DNAにて多重イオン化プロセスを考慮していないことに起因していると考えた。

第2章では新たに多重イオン化の物理、物理化学、化学プロセスを開発し、拡張機能としてGeant4-DNA version 10.07.p01に組み込み計算を行った。多重イオン化プロセスを考慮することで、これまで再現できなかったLETが200eV/nmを超える領域におけるH2O2のG値の実験値を再現することに成功した。また、多重イオン化プロセスを考慮することで、空気を含まない水においても放射線分解により生成した化学種同士の反応から酸素が形成されることが確認でき、先行研究で指摘されていた「トラック内酸素仮説」と一致する結果が得られた。

水の放射線分解生成種はLETだけではなく照射するイオン種の影響も受けるため、たとえLETが等しい場合でもイオン種が異なる場合、OHラジカル、水和電子、H2O2のG値は異なることが知られている。LETに代わるパラメータとして(Zeff/β)2を用いることで、異なるイオン線照射に対する差異が小さくなりシミュレーションで得られたG値を統一的に表すことができる可能性が示された。

粒子線がん治療において、生物学的影響に寄与する放射線分解により生じる化学種(ラジカルなど)の挙動をモンテカルロシミュレーションによって精度よく考慮できる治療計画が実現すれば、治療効果を最大化するだけでなく、周囲の正常組織への影響を最小限にとどめることができる可能性があるため、医療被ばくを抑えるという観点からも大きな意義をもつ研究となることが期待できる。

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