Flow cytometry, MRI, PET and NMR spectroscopy methods of non-invasive drug monitoring in prostate tumor

PET and MW images of mouse prostate tumors were correlated with histology, flow cytometry, DNA fragmentation analysis and NMR peaks. Hypotheses were: 1. signal intensities of intracellular sodium (/spl mu/MRI) and flouro-2-deoxy-glucose utilization (/spl mu/PET) increased in tumors; 2. image signal intensities were associated with apoptosis as result of DNA fragmentation and accumulation of NMR visible metabolites.PC-3 cell lines were compared with DU-145, LNCaP cell lines in culture for the [Na]/sub i/ and [Ca]/sub l/ ion sensing dyes, cell death NMR peaks and apoptosis staining for chemotherapeutic action of different drugs. After PC3 tumor imaging, taxotere (40 mg/kg; n=5) and VP-16 etoposide (1.2 mg/kg; n=7) was administered i.v. and imaging was done after 12 hours and 24 hours. Tumors were taken out for immunohistological staining by pentachrome, feulgen and ss-DNA antibody. /spl mu/PET and /spl mu/MRI images showed increased 18-FDG uptake and sodium signal intensities in tumor. In tumors, taxotere induced an increase in IC-Na 30 % (p<0.001) increase after 24 hours. FDG uptake increased 15 %(p<0.001) with decreased tumor size (10 %; p<0.001) than that of control tumors after 24 hours. Histological features were analyzed for high tumor risk (high ´IC/EC ratio´, high mitotic index and apoptotic index), decreased tumor viability (reduced mitotic figures, reduced diploidy or aneuploidy and proliferation index). These features in co-registered IC-Na, /spl mu/PET hypermetabolic and monoclonal antibody (ss-DNA) sensitive regions were identified that showed (% difference > 6 %). Sodium NMR peaks isolated intracellular sodium. Apoptosis rich regions showed characteristic nuclei with S phase DNA histogram, appearing brighter on IC-Na images and mild active on PET images. /sup 31/P-NMR spectra showed characteristic high phospho-choline peaks. Integrated sodium MRI and PET imaging, NMR peaks indicated apoptosis and offers in vivo drug monitoring method.