Targeted dendrimer-based contrast agents for articular cartilage assessment by MR imaging

Magnetic resonance (MR) imaging with contrast media has shown promise for articular cartilage assessment. Dendrimer-linked nitroxides, a new family of MR contrast agents targeted to glycosaminoglycan, may improve cartilage evaluation. This study is designed to determine the ability of dendrimer-linked nitroxides to enhance articular cartilage and measure the intra-articular life-time of these agents.

Cartilage T(1) was evaluated using immature bovine patella in solutions of five different dendrimer-linked nitroxides, saline or Gd-DTPA at 1.5T. The "relaxivity per dose" (change in cartilage 1/T(1) produced by a given concentration of agent) was calculated. The half-life of joint fluid enhancement was measured at 2T after solutions of three dendrimer-linked nitroxides, Gd-DTPA, and saline were injected into rabbit stifle joints. Twenty-four hours after injection, the joints were examined grossly and by histology for toxicity.

All but the largest dendrimer-linked nitroxide were able to intensely enhance articular cartilage on MR. Relaxivity per dose measurements were between 3.5 and 68 times greater than Gd-DTPA. The largest nitroxide appeared to be excluded from articular cartilage. Intra-articular half-lives of the dendrimer-linked nitroxides were sufficiently long (160-208 min) for in vivo MR imaging to be performed. Histological assessments of joints showed minimal synovial inflammatory and necrosis scores 1 day post-injection that were similar for all agents, including Gd-DTPA.

Dendrimer-linked nitroxides strongly enhance cartilage and are promising as articular cartilage-specific MR contrast agents. The intra-articular life-time is sufficient for imaging studies and, in initial evaluation, the agents exhibit minimal toxicity in rabbit joints.