Targeted dendrimer-based contrast agents for articular cartilage assessment by MR imaging 1

SummaryObjectiveMagnetic 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.DesignCartilage T1 was evaluated using immature bovine patella in solutions of five different dendrimer-linked nitroxides, saline or Gd–DTPA at 1.5 T. The “relaxivity per dose” (change in cartilage 1/T1 produced by a given concentration of agent) was calculated. The half-life of joint fluid enhancement was measured at 2 T 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.ResultsAll 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.ConclusionDendrimer-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.