title: MR lymphangiography with intradermal gadofosveset and human serum albumin in mice and primates.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Molecular Imaging Program, NCI, NIH, Bethesda, Maryland, USA.
authors.forename: Takahito
authors.initials: T
authors.lastname: Nakajima
authors.forename: Baris
authors.initials: B
authors.lastname: Turkbey
authors.forename: Kohei
authors.initials: K
authors.lastname: Sano
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Sato
authors.forename: Marcelino
authors.initials: M
authors.lastname: Bernardo
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hoyt
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage; D050091:Dendrimers / Q000008:administration & dosage; D005682:Gadolinium / Q000008:administration & dosage*; D019786:Gadolinium DTPA / Q000008:administration & dosage; D006801:Humans; D007271:Injections, Intradermal; D008198:Lymph Nodes / Q000033:anatomy & histology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000008:administration & dosage*; D012453:Saimiri; D012709:Serum Albumin / Q000008:administration & dosage*; D059629:Signal-To-Noise Ratio
chemical_list: D003287:Contrast Media; D050091:Dendrimers; D009942:Organometallic Compounds; D012709:Serum Albumin; D005682:Gadolinium; D019786:Gadolinium DTPA; C109932:gadofosveset trisodium
keywords: Gadofosveset; MR lymphangiography; contrast agents; lymphatic drainage; sentinel lymph node