CYCLOCREATINE ACCUMULATION LEADS TO CELLULAR SWELLING IN C6 GLIOMA MULTICELLULAR SPHEROIDS - DIFFUSION AND ONE-DIMENSIONAL CHEMICAL-SHIFT NUCLEAR-MAGNETIC-RESONANCE MICROSCOPY

Cyclocreatine, an analogue of creatine, inhibits tumor cell proliferat ion ill vitro and in vivo, The effects of cyclocreatine in large C6 gl ioma multicellular spheroids were mapped here by magnetic resonance mi croscopy, Diffusion-weighted images of C6 glioma spheroids resolved th e bright viable rim and the dark necrotic center, Sequential sets of d iffusion images, following cyclocreatine administration, showed increa sing self-diffusion coefficients of the intracellular water in the via ble rim (0.49 x 10(-5) cm(2)/s for untreated spheroids, 0.62 x 10(-5) cm(2)/s after 48 h perfusion with 20 mM cyclocreatine), This fact corr elated with cellular swelling apparent in histological sections. The r adial distribution of cyclocreatine and soluble lipids across perfused C6 spheroids was measured by one-dimensional chemical shift imaging, Cyclocreatine accumulation was prominent throughout the viable cell la yer, with no cyclocreatine accumulation In the necrotic center, In bot h cyclocreatine-treated and control spheroids the lipid signal was hig hest in the necrotic center and lower in the inner viable cell layer.