human tumor cell proliferation evaluated using manganese-enhanced mri人类肿瘤细胞增殖使用manganese-enhanced mri评估.pdfVIP

Human Tumor Cell Proliferation Evaluated Using Manganese-Enhanced MRI 1,2 1 1 1 1,3 Rod D. Braun *, David Bissig , Robert North , Kerry S. Vistisen , Bruce A. Berkowitz 1 Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America, 2 Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, United States of America, 3 Kresge Eye Institute, Wayne State University, Detroit, Michigan, United States of America Abstract Background: Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn2+ [measured with manganese-enhanced MRI (MEMRI)], is linked to proliferation rate in vitro. Methodology/Principal Findings: Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl2 for one hour and then thoroughly washed. MEMRI R1 values (longitudinal relaxation rates), which have a positive linear relationship with Mn2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn2+-induced increases in R1 compared to cells not exposed to Mn2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R1 values and proliferation rate (p#0.005), while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these