A model system of a paramagnetic lymphotropic MR contrast agent (Gd-DTPA labeled polyglucose associated macrocomplex, PGM) for T1-weighted MR imaging of lymph nodes in rats and rabbits was evaluated. Pharmacokinetic (tissue accumulation) and MR imaging data (optimal dose and timing parameters) were obtained in normal rats (n = 88) after subcutaneous (SC) injection of paramagnetic, radiolabeled [111In]Gd-DTPA-PGM. A rabbit model of lymph node metastases (n = 8) was ultimately used to demonstrate the potential of MR imaging with Gd-DTPA-PGM for nodal tumor detection. Maximum concentrations of Gd-DTPA-PGM were found in popliteal and paraaortic lymph nodes within 24 h after SC administration, and highest lymph node SNR values were obtained by MR imaging at this time point. The optimum imaging dose was 6-12 mumol Gd/kg. Tumor-lymph node contrast increased from 0.0 +/- 1.2 precontrast to 19.2 +/- 6.5 (spoiled gradient echo sequence, TR 50/TE 7/flip angle 60 degrees) postcontrast and conspicuity of nodal metastases was improved. Gd-DTPA-PGM accumulates in lymph nodes after SC administration and significantly enhances lymph node signal intensity of normal animals but not metastatic lymph nodes.