Abstract
BackgroundSodium weighted images can indicate sodium signal intensities from different features in the tumor before and 24 hours following administration of Taxotere.AimTo evaluate the association of in vivo intracellular sodium magnetic resonance image intensities with immuno-biomarkers and histopathological features to monitor the early tumor response to Taxotere chemotherapy in Methyl-Nitroso-Urea induced rat xenograft breast tumors.Methods and MaterialsMethyl-Nitroso-Urea (MNU) induced rat xenograft breast tumors were imaged for sodium MRI and compared with tumor histology, immunostaining after 24 hours chemotherapy.ResultsSodium MRI signal intensities represented sodium concentrations. Excised tumor histological sections showed different in vitro histological end points i.e. single strand DNA content of cell nuclei during cell cycle (G1/S-G2/M), distinct S or M histograms (Feulgen labeling to nuclear DNA content by CAS 200), mitotic figures and apoptosis at different locations of breast tumors. Necrosis and cystic fluid appeared gray on intracellular (IC) sodium images while apoptosis rich regions appeared brighter on IC sodium images. After 24 hours Taxotere-treated tumors showed lower 'IC/EC ratio' of viable cells (65–76%) with higher mitotic index; apoptotic tumor cells at high risk due to cytotoxicity (>70% with high apoptotic index); reduced proliferation index (270 vs 120 per high power field) associated with enhanced IC sodium in vivo MR image intensities and decreased tumor size (3%; p < 0.001; n = 16) than that of pre-treated tumors. IC-Na MR signal intensities possibly indicated Taxotere chemosensitivity response in vivo associated with apoptosis and different pre-malignant features within 24 hours of exposure of cancer cells to anti-neoplastic Taxotere drug.ConclusionSodium MRI imaging may be used as in vivo rapid drug monitoring method to evaluate Taxotere chemosensitivity response associated with neoplasia, apoptosis and tumor histology features.
Highlights
In tissue, sodium exists as total extracellular sodium (ECNa) ~ 139 mM occupying ~0.15 extracellular water spaces and bound intracellular sodium (IC-Na) ~ 15 mM concentrations
Sodium MRI imaging may be used as in vivo rapid drug monitoring method to evaluate Taxotere chemosensitivity response associated with neoplasia, apoptosis and tumor histology features
Tumor areas were delineated on single quantum (SQ) and inversion recovery (IR) sodium MR images using Optimas 6.5 software and their intracellular sodium was measured by relative signal intensity of known sodium concentration i.e. 1 M in 4% agarose phantom for determination of intracellular [Na]i
Summary
Sodium exists as total extracellular sodium (ECNa) ~ 139 mM occupying ~0.15 extracellular water spaces and bound intracellular sodium (IC-Na) ~ 15 mM concentrations. Tissue sodium concentrations may change during early tumor stages without membrane damage. Heterogeneous tumors showed the enhanced sodium MR image signal and sodium concentration in tumors [2,3]. Increased intracellular sodium along with histopathology and apoptosis related cytomorphological changes can provide the real time information of antineoplastic effects to optimize chemotherapeutic efficacy at the onset [2,4,5]. Docetaxal has gained attention for its cytotoxic effect in cancer prevention. Rapid time-dependent monitoring of docetaxal chemosensitivity by sodium MRI is emerging as clinical tool in cancer therapy [2,5]. Sodium weighted images can indicate sodium signal intensities from different features in the tumor before and 24 hours following administration of Taxotere
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