Preliminary evaluation of a polyethyleneglycol‐stabilized manganese‐substituted hydroxylapatite as an intravascular contrast agent for MR angiography

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Abstract
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. Halflives (with amplitudes in parenthesis) were 4 ± 1 minutes (55%), and 49 ± 3 minutes (45%), respectively, for the two phases. A dose of 40 μmol 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.