title: Preliminary evaluation of a polyethyleneglycol-stabilized manganese-substituted hydroxylapatite as an intravascular contrast agent for MR angiography.
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. 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.
authors.affiliation: Medical Imaging Division, Mallinckrodt, Inc., St. Louis MO, USA.
authors.forename: K
authors.initials: K
authors.lastname: Adzamli
authors.forename: R B
authors.initials: RB
authors.lastname: Dorshow
authors.forename: M R
authors.initials: MR
authors.lastname: Hynes
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: D L
authors.initials: DL
authors.lastname: Nosco
authors.forename: M D
authors.initials: MD
authors.lastname: Adams
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage; D004355:Drug Stability; D017886:Durapatite / Q000737:chemistry*; D005069:Evaluation Studies as Topic; D006207:Half-Life; D006882:Hydroxyapatites / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008345:Manganese / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011817:Rabbits; D013499:Surface Properties
chemical_list: D003287:Contrast Media; D006882:Hydroxyapatites; D011092:Polyethylene Glycols; D008345:Manganese; D017886:Durapatite