Abstract
PURPOSE: To investigate MR lymphangiography in mice and primates with intradermal Gadofosveset and human serum albumin. Gadofosveset is a US FDA approved small molecule Gadolinium (Gd) chelate (957 Da) which reversibly binds serum albumin and temporally behaves as a macromolecule. As the structure of albumin varies among species, the affinity of Gadofosveset is optimized for human albumin. In this study, Gadofosveset premixed with 10% human serum albumin (HSA) was injected intradermally in mice and monkeys, and then MR lymphangiography was performed on a 3.0 Tesla clinical scanner. MATERIALS AND METHODS: Twenty microliters of each agent was injected intradermally at both sides of the front and back paws using a 30-gauge needle into female athymic nude mice (6-8 weeks old, n = 3 mice in each group). The performance of Gadofosveset-HSA was compared with Gd-labeled dendrimers (G4: 6 nm, G6: 10 nm) or Gd-DTPA. The target-to-muscle ratio (TMR = target signal intensity (SI)/muscle SI) was calculated at each time point. The TMRs were compared with a one-way analysis of variance followed by a Bonferroni multiple comparison test. RESULTS: Images taken as early as 2.5 min after intradermal (id) injection depicted enhanced lymph nodes using Gadofosveset-HSA (2.41 ± 0.20). Up to 7.5 min after injection, TMRs of Gadofosveset-HSA were greater than those of dendrimers (G4 or G6-Gd-DTPA: 2.24 ± 0.10, 2.12 ± 0.11, respectively). By 15 min postinjection, TMRs of Gadofosveset-HSA (2.18 ± 0.19) were comparable to Gd-labeled dendrimers (G4-Gd-DTPA: 2.37 ± 0.15, G6-Gd-DTPA: 2.25 ± 0.18). Gadofosveset-HSA and Gd labeled dendrimers resulted in satisfactory MR lymphography in mice and monkeys. CONCLUSION: Because both Gadofosveset and HSA are approved for human use and Gadofosveset clears rapidly through the kidneys, this method has advantages over Gd-dendrimers and could be used for visualizing lymphatic drainage and detecting lymph nodes.