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Molecular imaging coupled to pattern recognition distinguishes response to temozolomide in preclinical glioblastoma.
- Source :
-
NMR in biomedicine [NMR Biomed] 2014 Nov; Vol. 27 (11), pp. 1333-45. Date of Electronic Publication: 2014 Sep 10. - Publication Year :
- 2014
-
Abstract
- 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.<br /> (Copyright © 2014 John Wiley & Sons, Ltd.)
- Subjects :
- Animals
Antineoplastic Agents, Alkylating administration & dosage
Antineoplastic Agents, Alkylating analysis
Antineoplastic Agents, Alkylating pharmacokinetics
Apoptosis
Brain metabolism
Brain Neoplasms chemistry
Brain Neoplasms pathology
Cell Line, Tumor
Dacarbazine administration & dosage
Dacarbazine analysis
Dacarbazine pharmacokinetics
Dacarbazine therapeutic use
Drug Administration Schedule
Female
Glioblastoma chemistry
Glioblastoma pathology
Metabolome
Mice
Mice, Inbred C57BL
Mitosis
Temozolomide
Tumor Burden
Antineoplastic Agents, Alkylating therapeutic use
Brain Neoplasms drug therapy
Dacarbazine analogs & derivatives
Glioblastoma drug therapy
Magnetic Resonance Imaging methods
Magnetic Resonance Spectroscopy methods
Pattern Recognition, Automated
Subjects
Details
- Language :
- English
- ISSN :
- 1099-1492
- Volume :
- 27
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- NMR in biomedicine
- Publication Type :
- Academic Journal
- Accession number :
- 25208348
- Full Text :
- https://doi.org/10.1002/nbm.3194