title: A low molecular weight folate receptor targeted contrast agent for magnetic resonance tumor imaging.
abstract: OBJECTIVE
  This study aims to develop a low molecular weight folate receptor (FR) contrast agent for MR tumor imaging.
  
  
  METHODS
  Gadolinium-tetraazacyclododecane tetraacetic acid (Gd.DOTA) was conjugated to folic acid to create Gd.DOTA.Folate. The efficacy of Gd.DOTA.Folate to bind FR was evaluated in vitro by inductively coupled mass spectrometry (ICP-MS) and in vivo by magnetic resonance imaging (MRI) tumor enhancement over 14 h, utilizing an overexpressing α-FR cell line (IGROV-1), compared to an α-FR-negative cell line (OVCAR-3). Gd.DOTA.Folate localization ex vivo was verified by laser ablation ICP-MS.
  
  
  RESULTS
  ICP-MS confirmed Gd.DOTA.Folate uptake by IGROV-1 cells and competitive binding with free folic acid inhibited binding. IGROV-1 tumors showed an increase in R (1) at 2 h, which increased significantly over 14 h post-Gd.DOTA.Folate with clear enhancement on MR images. This was not observed in controls.
  
  
  CONCLUSIONS
  These data support the use of FR-targeted small molecular weight MRI contrast agents for tumor imaging in vivo.
authors.affiliation: MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, UK. tammy.kalber@csc.mrc.ac.uk
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Kalber
authors.forename: Nazila
authors.initials: N
authors.lastname: Kamaly
authors.forename: Po-Wah
authors.initials: PW
authors.lastname: So
authors.forename: John A
authors.initials: JA
authors.lastname: Pugh
authors.forename: Josephine
authors.initials: J
authors.lastname: Bunch
authors.forename: Cameron W
authors.initials: CW
authors.lastname: McLeod
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jorgensen
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Bell
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D005492:Folic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D005682:Gadolinium / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D013194:Staining and Labeling
chemical_list: D003287:Contrast Media; D058973:Folate Receptors, GPI-Anchored; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D005492:Folic Acid; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D005682:Gadolinium
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