Lymph node staging using dedicated magnetic resonance contrast agents--the accumulation mechanism revisited

When diagnosing cancer, assessing the nodal stage is tremendously important in determining the patient's prognosis. Computed tomography (CT) and magnetic resonance (MR) imaging (MRI) assessments of the regional lymph node (LN) size and shape are currently used for the initial nodal staging in clinical settings, although this approach has a rather low sensitivity, and biopsy often leads to restaging of the LNs. Acknowledging the great medical need to accurately stage LNs, scientists and clinicians have been working since the late 1980s on MR contrast agents that provide more reliable staging results. Different types of molecules (i.e., iron oxide nanoparticles and Gd-based contrast agent) have shown promising LN accumulation and imaging results, but no clinically approved, dedicated LN staging contrast agent is currently available. The literature describes a mechanism of contrast agent accumulation in the LNs that considers some but not all published experimental evidence. However, confidence in the mechanism of LN accumulation is a prerequisite for the directed synthesis of compounds for accurate and sensitive LN staging. To improve our understanding of the LN contrast agent accumulation mechanism, we reviewed the published data on the enrichment of colloidal MR contrast agent candidates in LNs, and we suggest an extended mechanism for contrast agent enrichment in LNs. For further clarification, physiology and results from drug targeting studies are considered where applicable.