David A. Kovar

Fast spectroscopic imaging of water and fat resonances to improve the quality of MR images

RATIONALE AND OBJECTIVES The authors evaluated whether fast spectroscopic imaging of water and fat resonances can produce high-quality anatomic magnetic resonance (MR) images of rodent tumors and human breast. MATERIALS AND METHODS Fast MR spectroscopic images of eight rats with mammary tumors were acquired by using a 4.7-T MR unit equipped with self-shielded gradient coils. MR spectroscopic images of four human breasts were acquired with a 1.5-T MR unit. RESULTS Artifacts due to eddy currents were minimal. Images synthesized from MR spectroscopic data, in which intensity was proportional to water signal peak height, were similar to T2-weighted MR images. Boundaries of rodent mammary tumors are similar but not identical on peak height-weighted and T2-weighted images. MR spectroscopic images of human breast showed improved detail compared to gradient-echo MR images. CONCLUSION Preliminary results suggest that incorporation of fast MR spectroscopic imaging methods into many standard clinical MR imaging procedures may substantially improve image quality.

In vitro evaluation of calphostin C as a novel agent for photodynamic therapy of bladder cancer

OBJECTIVES Calphostin C, a highly specific protein kinase C inhibitor, induces apoptosis in the presence of visible light. We report the photoactivatable cytotoxicity of calphostin C in a series of well-characterized human bladder cancer cell lines: RT4, UM-UC-3, and 5637. METHODS The human bladder cancer cell lines RT4, UM-UC-3, and 5637 were chosen on the basis of their p53, pRb and 9p21 deletion status. Using standard tissue culture techniques, the cytotoxicity of 10 to 100 nM calphostin C in combination with increasing exposures of visible light was examined. Controls consisted of cells treated with calphostin C without visible light and cells exposed to visible light without calphostin C treatment. Cell viability was determined by MTT assay. The induction of apoptosis by activated calphostin C was determined by 4,6-diamidino-2-phenylindole (DAPI) staining/fluorescence microscopy of nuclei. RESULTS In the absence of light, calphostin C did not demonstrate a cytotoxic effect on any of the cell lines tested. Increasing the duration of light exposure resulted in a concomitant decrease in cell viability. Significant cell death was seen with calphostin C concentrations as low as 10 nM. These studies also demonstrated that calphostin C induced apoptosis by a mechanism independent of p53 and pRb status and the presence or absence of 9p21 deletions. CONCLUSIONS We demonstrated the ability of activated calphostin C to induce apoptosis in a light-dependent and concentration-dependent fashion in a bladder cancer model system. Activated calphostin C cytotoxicity is independent of tumor genetic background and the status of p53 and pRb. Further development of calphostin C as a photosensitizer for photodynamic therapy of superficial bladder cancer may be warranted.