Taxotere Chemosensitivity Evaluation in Mice Prostate Tumor: Validation and Diagnostic Accuracy of Quantitative Measurement of Tumor Characteristics by MRI, PET, and Histology of Mice Tumor

Abstract

Increased PET and MRI image intensities of mouse prostate tumors were correlated with histostaining tumor characteristics. The hypothesis was that increased intracellular sodium microMRI signal intensities and flouro-2-deoxy-glucose utilization by microPET in apoptosis rich regions in tumors were positively correlated as chemosensitivity assay of Taxotere. The PC-3 cancer cell line induced prostate tumor MRI and PET images and histology slices were digitally captured and compared in pre- and post-Taxotere treated tumors. The optimization of inversion recovery MRI parameters was done to generate sodium images of phantom. The (18)FDG biotransformation was optimized to measure PET image intensities. A criterion was developed to evaluate malignancy by histology. For correlation, regression analysis was done using imaging, histology, and immunostaining data from PC3 tumor after 24 and 48 hours post-Taxotere treatment. Apoptosis indices were calculated by histostaining and ss-DNA antibody assay. Sodium MRI and PET signal intensity distributions were comparable at specific locations relatively and measured in tumor tissue regions. In tumors, Taxotere induced an increase in intracellular sodium MRI signal 30% (p<0.001) with decreased tumor size (20%; p<0.001) and micro-PET showed FDG uptake increase 15% (p<0.001) with decreased tumor size (10%; p<0.001) than that of control tumors after 24 hours. Histological features indicated tumor risk (high 'intracellular/extracellular ratio', high mitotic index, and apoptotic index), decreased tumor viability (reduced mitotic figures, reduced diploidy or aneuploidy, and proliferation index) after Taxotere treatment. These features in co-registered intracellular sodium, microPET hypermetabolic, and monoclonal antibody (ss-DNA) sensitive regions showed (% difference > 6%). Apoptosis rich regions showed characteristic nuclei with S phase DNA histogram, appearing brighter on IC-Na images and mild active on PET images (sensitivity=65%; specificity=70%). In conclusion, MRI and PET multimodal imaging may be rapid non-invasive chemosensitivity assay to monitor the drug anticancer effect.