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Imaging of branched chain amino acid metabolism in tumors with hyperpolarized 13C ketoisocaproate.
Karlsson, Magnus; Jensen, Pernille R; in 't Zandt, René; Gisselsson, Anna; Hansson, Georg; Duus, Jens Ø; Meier, Sebastian; Lerche, Mathilde H.
Afiliação
  • Karlsson M; Imagnia AB, Box 8225, 200 41 Malmö, Sweden.
Int J Cancer ; 127(3): 729-36, 2010 Aug 01.
Article em En | MEDLINE | ID: mdl-19960440
Powerful analytical tools are vital for characterizing the complex molecular changes underlying oncogenesis and cancer treatment. This is particularly true, if information is to be collected in vivo by noninvasive approaches. In the recent past, hyperpolarized (13)C magnetic resonance (MR) spectroscopy has been employed to quickly collect detailed spectral information on the chemical fate of tracer molecules in different tissues at high sensitivity. Here, we report a preclinical study showing that alpha-ketoisocaproic acid (KIC) can be used to assess molecular signatures of tumors with hyperpolarized MR spectroscopy. KIC is metabolized to leucine by the enzyme branched chain amino acid transferase (BCAT), which is found upregulated in some tumors. BCAT is a putative marker for metastasis and a target of the proto-oncogene c-myc. Very different fluxes through the BCAT-catalyzed reaction can be detected for murine lymphoma (EL4) and rat mammary adenocarcinoma (R3230AC) tumors in vivo. EL4 tumors show a more than 7-fold higher hyperpolarized (13)C leucine signal relative to the surrounding healthy tissue. In R3230AC tumor on the other hand branched chain amino acid metabolism is not enhanced relative to surrounding tissues. The distinct molecular signatures of branched chain amino acid metabolism in EL4 and R3230AC tumors correlate well with ex vivo assays of BCAT activity.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenocarcinoma / Aminoácidos / Cetoácidos / Neoplasias Mamárias Experimentais Limite: Animals Idioma: En Revista: Int J Cancer Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Suécia País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenocarcinoma / Aminoácidos / Cetoácidos / Neoplasias Mamárias Experimentais Limite: Animals Idioma: En Revista: Int J Cancer Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Suécia País de publicação: Estados Unidos