Details

Autor(en) / Beteiligte

• Jensen, Pernille R.
• Serra, Sonia Colombo
• Miragoli, Luigi
• Karlsson, Magnus
• Cabella, Claudia
• Poggi, Luisa
• Venturi, Luca
• Tedoldi, Fabio
• Lerche, Mathilde H.

Titel

Hyperpolarized [1,3‐13C2]ethyl acetoacetate is a novel diagnostic metabolic marker of liver cancer

Ist Teil von

• International journal of cancer, 2015-02, Vol.136 (4), p.E117-E126

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2015

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• An increased prevalence of liver diseases such as hepatitis C and nonalcoholic fatty liver results in an augmented incidence of the most common form of liver cancer, hepatocellular carcinoma (HCC). HCC is most often found in the cirrhotic liver and it can therefore be challenging to rely on anatomical information alone when diagnosing HCC. Valuable information on specific cellular metabolism can be obtained with high sensitivity thanks to an emerging magnetic resonance (MR) technique that uses 13C labeled hyperpolarized molecules. Our interest was to explore potential new high contrast metabolic markers of HCC using hyperpolarized 13C‐MR. This work led to the identification of a class of substrates, low molecular weight ethyl‐esters, which showed high specificity for carboxyl esterases and proved in many cases to possess good properties for signal enhancement. In particular, hyperpolarized [1,3‐13C2]ethyl acetoacetate (EAA) was shown to provide a metabolic fingerprint of HCC. Using this substrate a liver cancer implanted in rats was diagnosed as a consequence of an ∼4 times higher metabolic substrate‐to‐product ratio than in the surrounding healthy tissue, (p = 0.009). Unregulated cellular uptake as well as cosubstrate independent enzymatic conversion of EAA, made this substrate highly useful as a hyperpolarized 13C‐MR marker. This could be appreciated by the signal‐to‐noise (SNR) obtained from EAA, which was comparable to the SNR reported in a literature liver cancer study with state‐of‐the‐art hyperpolarized substrate, [1‐13C]pyruvate. Also, the contrast‐to‐noise (CNR) in the EAA based metabolic ratio images was significantly improved compared with the CNR in equivalent images reported using [1‐13C]pyruvate. What's New? An emerging approach to metabolic imaging in cancer is based on 13C‐hyperpolarized magnetic resonance (MR) spectroscopy. But metabolic markers specific to cancer must be identified to realize its promise. Here, metabolic conversion of hyperpolarized esters was explored as a potential means of detecting hepatocellular carcinoma (HCC). Hyperpolarized [1,3‐13C2]ethyl acetoacetate (EAA) was found to be an exceptionally good substrate for carboxyl esterase‐1, concentrations and activities of which are altered in cancer cells. Metabolic conversion of EAA as a substrate for 13C‐hyperpolarized MR significantly enhanced the detection of implanted liver cancer in rats.