PRELIMINARY EVALUATION OF A POLYETHYLENEGLYCOL-STABILIZED MANGANESE-SUBSTITUTED HYDROXYLAPATITE AS AN INTRAVASCULAR CONTRAST AGENT FOR MR-ANGIOGRAPHY

A blood-persistent particulate paramagnetic contrast agent has been fo rmulated via size stabilization of manganese-substituted hydroxylapati te by a polyethylene glycol (PEG) bearing a terminal diphosphonate. At high PEG surface densities (35-40 mol %), particles with mean diamete r 8 +/- 2 nn were obtained. Relaxivities of antoclaved samples (at 20 MHz proton Lamor frequency) were R1 = 18.7 +/- .8 mM(-1) sec(-1) and R 2 = 22.3 +/- .7 mM(-1) sec(-1). The formulation persisted in rabbit bl ood with a biphasic clearance profile. Half-lives (with amplitudes in parenthesis) were 4 +/- 1 minutes (55%), and 49 +/- 3 minutes (45%), r espectively, for the two phases. A dose of 40 mu mol Mn/kg body weight enhanced the signal from rabbit vasculature for more than 45 minutes on MR angiograms. Thus, PEG-modified MnHA particles may find use as T1 agents for MR angiography.