JP2010529868A - 過分極13c−ピルビン酸塩を含むmr造影剤を用いて腫瘍のグレーディングを行うmr方法 - Google Patents
過分極13c−ピルビン酸塩を含むmr造影剤を用いて腫瘍のグレーディングを行うmr方法 Download PDFInfo
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Abstract
【選択図】図6
Description
a)過分極13C−ピルビン酸塩を含む造影剤を用いて被験体における腫瘍のMR検出を行う段階であって、13C−ピルビン酸塩並びにその13C含有代謝産物であるアラニン、乳酸塩及び任意には重炭酸塩の信号を検出する段階と、
b)前記信号及び任意には総炭素信号を用いて腫瘍の代謝プロファイルを生成する段階と、
c)段階b)で生成した腫瘍の代謝プロファイルを特定グレードの腫瘍の既知代謝プロファイルと比較する段階と、
d)腫瘍の前記代謝プロファイルと前記既知代謝プロファイルとの類似点及び相違点に基づいて腫瘍のグレードを決定する段階と
を含んでなる方法を提供する。
a)過分極13C−ピルビン酸塩を含む造影剤を用いて被験体における腫瘍のMR検出を行う段階であって、13C−ピルビン酸塩並びにその13C含有代謝産物であるアラニン、乳酸塩及び任意には重炭酸塩の信号を検出する段階と、
b)前記信号及び任意には総炭素信号を用いることで、かかる信号と腫瘍グレードとの関係を示す標準曲線から腫瘍のグレードを決定する段階と
を含んでなる方法である。
本発明の文脈中における「腫瘍のグレード」という用語は、前記腫瘍の攻撃性及び/又は悪性度の認知される程度をいう。
a)過分極13C−ピルビン酸塩を含む造影剤を用いて被験体における腫瘍のMR検出を行う段階であって、13C−ピルビン酸塩並びにその13C含有代謝産物であるアラニン、乳酸塩及び任意には重炭酸塩の信号を検出する段階と、
b)前記信号及び任意には総炭素信号を用いて腫瘍の代謝プロファイルを生成する段階と、
c)段階b)で生成した腫瘍の代謝プロファイルを特定グレードの腫瘍の既知代謝プロファイルと比較する段階と、
d)腫瘍の前記代謝プロファイルと前記既知代謝プロファイルとの類似点及び相違点に基づいて腫瘍のグレードを決定する段階と
を含んでなる方法を提供する。
a)過分極13C−ピルビン酸塩を含む造影剤を用いて被験体における腫瘍のMR検出を行う段階であって、13C−ピルビン酸塩並びにその13C含有代謝産物であるアラニン、乳酸塩及び任意には重炭酸塩の信号を検出する段階と、
b)前記信号を用いることで、かかる信号と腫瘍グレードとの関係を示す標準曲線から腫瘍のグレードを決定する段階と
を含んでなる方法である。
正常マウス(N=5)及びTRAMPマウス(N=4初期原発腫瘍(低グレード腫瘍)、N=5後期原発腫瘍(高グレード腫瘍)に関するすべての研究は、UCSF Institutional Animal Care and Utilization Committeeによって承認されたプロトコル(1)の下で実施した。この研究に含まれるすべてのマウスについては、過分極MR検査の1日以上前に、頸部の背面から延びる28gのポートを一方の頸静脈中に外科的に植え込んだ。MR実験に際しては、マウスを1〜1.5%のイソフルランで麻酔し、硬質プラスチックコネクター(Strategic Applications社、リバティービル、米国イリノイ州)を用いて長さ90cmの24g延長チューブを頸静脈ポートに連結した。この特殊延長チューブは、チューブ中に小さい死容積を維持しながら人体MRスキャナー内で過分極剤を急速に注入することを可能にした。次に、循環水によって約37℃に加熱した水充填式の恒温パッド上にマウスを載せ、特注の二重同調プロトン−炭素T/Rコイル内に配置した。コイルデザインは、5cmの内径、8cmの長さ、及びコイル内にいる間にマウスの目視監視を可能にするため上面に設けられた開放溝穴を有する1H直交コイル内の直交13Cコイルからなっていた。装置全体を患者テーブル上に載せ、多核分光法パッケージを備えた3Tヒト用GEスキャナーの内腔に配置した。
カスタムソフトウェアを用いてMRI/13C−MRSIデータを処理しかつ整頓した。病理学に基づいて同定した前立腺癌の原発領域及び転移領域を、対応する高空間分解能の解剖学的画像上にトレースした。検査対象の組織タイプに関連するすべてのボクセルを、各々の代謝産物に関し、所定の周波数範囲にわたって積分した。すべての積分は、いかなる代謝産物も含まないスペクトル領域から計算したノイズによってスケーリングした。所定の代謝産物及び組織タイプに関するスケーリング済み積分を各検査についてまとめて平均することで、1つの代謝プロファイル(即ち、各検査についての乳酸塩、アラニン及びピルビン酸塩数の集合)を得た。JMPを用いて様々な検査からの平均値を統計的に比較することで、データに関する分散分析を行った。統計的な有意差が見出された場合には、多重比較のためのターキィ(Tukey)補正を含むt検定を用いて4つの組織タイプをペア単位で比較した。加えて、同一動物からの多重検査を含むことによって導入されることがある何らかの相関関係を補正するため、すべての統計的検定中にランダムエフェクツ(Random Effects)モデルを組み込んだ。
図1ないし図4は、正常なマウス前立腺(図1)、TRAMPマウス前立腺中の初期原発腫瘍(図2)、後期原発腫瘍(図3)及びリンパ節転移領域(図4)から採取した代表的なT2重み付き軸方向画像(A)、選択された病理学に対応する0.135cc過分極13Cスペクトルを示すグリッドを重ね合わせたT2重み付き画像(B)、対応するスペクトル(C)、及びH&E染色組織切片(D)を示している。図1に見られる通り、正常なマウス前立腺は非常に小さな器官(約0.022cc)であり、周囲組織からのスペクトル寄与を最小にしながらマウス前立腺を包囲するボクセルを選択するように注意しなければならない。これは、ゼロ充填スペクトルデータ(ダッシュドボックス、真の分解能は実線である)がマウス前立腺に最大限に重なり合うまでそれをボクセルシフトさせることによる後処理で達成された(1B)。対応する過分極13Cスペクトル(1C)は、ピルビン酸塩(173ppm)並びにその代謝産物である乳酸塩(185ppm)及びアラニン(178ppm)に関する共鳴を示した。ピルビン酸塩共鳴が最大であり、それに続いて乳酸塩、アラニン、及びピルビン酸塩水和物に関する小共鳴が見られた。健常なヒト前立腺と同じく、マウス前立腺は、H&E切片で示されるように管を包囲する腺上皮細胞が支質組織により結合されてなる腺器官である(1D)。
Claims (9)
- 腫瘍のグレードを決定する方法であって、
a)過分極13C−ピルビン酸塩を含む造影剤を用いて被験体における腫瘍のMR検出を行う段階であって、13C−ピルビン酸塩並びにその13C含有代謝産物であるアラニン、乳酸塩及び任意には重炭酸塩の信号を検出する段階と、
b)前記信号及び任意には総炭素信号を用いて腫瘍の代謝プロファイルを生成する段階と、
c)段階b)で生成した腫瘍の代謝プロファイルを特定グレードの腫瘍の既知代謝プロファイルと比較する段階と、
d)腫瘍の前記代謝プロファイルと前記既知代謝プロファイルとの類似点及び相違点に基づいて腫瘍のグレードを決定する段階と
を含んでなる方法。 - 段階b)において乳酸塩の信号及び/又は総炭素信号が使用される、請求項1記載の方法。
- 既知代謝プロファイルが、過分極13C−ピルビン酸塩を含む造影剤を用いて被験体における腫瘍のMR検出を行って、13C−ピルビン酸塩並びにその13C含有代謝産物であるアラニン、乳酸塩及び任意には重炭酸塩の信号を検出し、前記信号及び任意には総炭素信号を用いて腫瘍の代謝プロファイルを生成することで得られたものである、請求項1及び請求項2記載の方法。
- 腫瘍のグレードを決定する方法であって、
a)過分極13C−ピルビン酸塩を含む造影剤を用いて被験体における腫瘍のMR検出を行う段階であって、13C−ピルビン酸塩並びにその13C含有代謝産物であるアラニン、乳酸塩及び任意には重炭酸塩の信号を検出する段階と、
b)前記信号及び任意には総炭素信号を用いることで、かかる信号と腫瘍グレードとの関係を示す標準曲線から腫瘍のグレードを決定する段階と
を含んでなる方法。 - 段階b)において乳酸塩の信号及び/又は総炭素信号が使用される、請求項4記載の方法。
- 当該方法が前立腺腫瘍のグレードを決定する方法である、請求項1ないし請求項5記載の方法。
- 腫瘍のグレードを決定する方法で使用されるMR造影剤を製造するための過分極13C−ピルビン酸塩の使用であって、前記方法が
a)過分極13C−ピルビン酸塩を含む前記造影剤を用いて被験体における腫瘍のMR検出を行う段階であって、13C−ピルビン酸塩並びにその13C含有代謝産物であるアラニン、乳酸塩及び任意には重炭酸塩の信号を検出する段階と、
b)前記信号及び任意には総炭素信号を用いて腫瘍の代謝プロファイルを生成する段階と、
c)段階b)で生成した腫瘍の代謝プロファイルを特定グレードの腫瘍の既知代謝プロファイルと比較する段階と、
d)腫瘍の前記代謝プロファイルと前記既知代謝プロファイルとの類似点及び相違点に基づいて腫瘍のグレードを決定する段階と
を含んでなる、使用。 - 腫瘍のグレードを決定する方法で使用されるMR造影剤を製造するための過分極13C−ピルビン酸塩の使用であって、前記方法が
a)過分極13C−ピルビン酸塩を含む造影剤を用いて被験体における腫瘍のMR検出を行う段階であって、13C−ピルビン酸塩並びにその13C含有代謝産物であるアラニン、乳酸塩及び任意には重炭酸塩の信号を検出する段階と、
b)前記信号及び任意には総炭素信号を用いることで、かかる信号と腫瘍グレードとの関係を示す標準曲線から腫瘍のグレードを決定する段階と
を含んでなる、使用。 - 前記方法が前立腺腫瘍のグレードを決定する方法である、請求項7及び請求項8記載の使用。
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