Details

Autor(en) / Beteiligte

• Delgado-Goñi, Teresa
• Julià-Sapé, Margarida
• Candiota, Ana Paula
• Pumarola, Martí
• Arús, Carles

Titel

Molecular imaging coupled to pattern recognition distinguishes response to temozolomide in preclinical glioblastoma

Ist Teil von

• NMR in biomedicine, 2014-11, Vol.27 (11), p.1333-1345

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2014

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Non‐invasive monitoring of response to treatment of glioblastoma (GB) is nowadays carried out using MRI. MRS and MR spectroscopic imaging (MRSI) constitute promising tools for this undertaking. A temozolomide (TMZ) protocol was optimized for GL261 GB. Sixty‐three mice were studied by MRI/MRS/MRSI. The spectroscopic information was used for the classification of control brain and untreated and responding GB, and validated against post‐mortem immunostainings in selected animals. A classification system was developed, based on the MRSI‐sampled metabolome of normal brain parenchyma, untreated and responding GB, with a 93% accuracy. Classification of an independent test set yielded a balanced error rate of 6% or less. Classifications correlated well both with tumor volume changes detected by MRI after two TMZ cycles and with the histopathological data: a significant decrease (p < 0.05) in the proliferation and mitotic rates and a 4.6‐fold increase in the apoptotic rate. A surrogate response biomarker based on the linear combination of 12 spectral features has been found in the MRS/MRSI pattern of treated tumors, allowing the non‐invasive classification of growing and responding GL261 GB. The methodology described can be applied to preclinical treatment efficacy studies to test new antitumoral drugs, and begets translational potential for early response detection in clinical studies. Copyright © 2014 John Wiley & Sons, Ltd. A surrogate response biomarker, based in the linear combination of 12 spectral features, has been found in the MRS/MRSI pattern of GB treated with TMZ. This spectroscopic information has been used to develop a non‐invasive classification system of tumor response to therapy, consistent and applicable to unseen cases. The early response biomarker can be used in future studies for evaluating the interest of new antitumoral drugs.