X-Ray Microscopy Studies on the Pharmaco-Dynamics of Therapeutic Gallium in Rat Bones

Abstract

Since the original observation of exogenous gallium accumulation in bones ANGHILERI et al. [1], several studies have demonstrated that gallium nitrate is extremely effective in preserving bone mineral content both in vivo and in vitro (WARRELL et al., [2]; BOCKMAN et al. [3]). Gallium nitrate therapy normalized serum calcium levels in a study of patients with cancer-related hypercalcemia, resistant to standard hydration and diuretic therapy. Recently, gallium nitrate treatment has been shown to halt the accelerated bone resorption that is frequently associated with cancers metastatic to bone (BOCKMAN et al. [4]). Several lines of evidence from in vitro studies (CHUN et al. [5]) recently led to the demonstration oîincreased bone calcium and improvement in hydroxyapatite crystallinity in adult gallium-treated rats (BOCKMAN et al. [6]). Evidence is rapidly accumulating that gallium nitrate is an effective, new therapeutic agent for inhibition of accelerated bone resorption associated with cancer-related hypercalcemia. It has also been suggested that gallium could have wide clinical applications in disorders characterized by accelerated calcium loss from bone (BOCKMAN et al. [6]). However, while gallium is known to accumulate in bone, the effects of gallium on the kinetics of bone calcium uptake and loss are unknown. Nor is it known in which compartments (epiphysis, metaphysis, diaphysis, endosteal or periosteal surfaces) the gallium metal is preferentially localized. Gross analytical measurements of gallium content have previously been performed on excised bone segments, but these lack precise spatial resolution. We describe here our preliminary results on gallium and calcium quantitation and localization using x-ray microscopy techniques at the X-26 beam line of the National Synchrotron Light Source (NSLS) at 50–100 μm resolution and 10⁻⁶ g/g detection levels.