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 formulated via size stabilization of manganese-substituted hydroxylapatite by a polyethylene glycol (PEG) bearing a terminal diphosphonate. At high PEG surface densities (35-40 mol%), particles with mean diameter 8 +/- 2 nm were obtained. Relaxivities of autoclaved samples (at 20 MHz proton Lamor frequency) were R1 = 18.7 +/- .8 mM-1 sec-1 and R2 = 22.3 +/- .7 mM-1 sec-1. The formulation persisted in rabbit blood with a biphasic clearance profile. Half-lives (with amplitudes in parenthesis) were 4 +/- 1 minutes (55%), and 49 +/- 3 minutes (45%), respectively, for the two phases. A dose of 40 mumol 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.