Inflammation: imaging with methoxy poly(ethylene glycol)-poly-L-lysine-DTPA, a long-circulating graft copolymer.

Abstract

To test whether a nontargeted, long-circulating, synthetic polymer accumulates in areas of inflammation, with high capillary permeability and increased regional blood flow. Methoxy poly(ethylene glycol)-poly-L-lysine (PL)-diethylenetriaminepentaacetic acid (MPEG-PL-DTPA) was labeled with technetium-99m for scintigraphy and with gadolinium for magnetic resonance (MR) imaging. Eleven Escherichia coli-infected rats were injected with 1.0 mCi (37 MBq) of Tc-99m-labeled MPEG-PL-DTPA for scintigraphy. Twelve rats underwent 1.5-T MR imaging after intravenous injection of gadolinium-labeled MPEG-PL-DTPA (35 mumol/kg). Tc-99m-labeled MPEG-PL-DTPA demonstrated nearly eight-fold higher accumulation in infected muscle when compared with normal muscle. Scintigrams and MR images showed areas of inflammation with peak accumulation at 24 hours after injection of Tc-99m- or gadolinium-labeled MPEG-PL-DTPA. Nontargeted, long-circulating, copolymers can efficiently accumulate in sites of inflammation and thus represent an alternative to inflammation-specific agents.