MR Lymphangiography With Intradermal Gadofosveset and Human Serum Albumin in Mice and Primates

作者：Nakajima Takahito; Turkbey Baris; Sano Kohei; Sato Kazuhide; Bernardo Marcelino; Hoyt Robert F; Choyke Peter L; Kobayashi Hisataka^*

来源：Journal of Magnetic Resonance Imaging, 2014, 40(3): 691-697.

DOI：10.1002/jmri.24395

• Gadofosveset
• MR lymphangiography
• sentinel lymph node
• contrast agents
• lymphatic drainage

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 GdDTPA. 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, G6Gd-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.

• 出版日期2014-9