title: P03277-A New Approach to Achieve High-Contrast Enhancement: Initial Results of an Experimental Extracellular Gadolinium-Based Magnetic Resonance Contrast Agent.
abstract: OBJECTIVE
  This study aims to compare the enhancement properties of an experimental high-relaxivity extracellular gadolinium chelate (P03277) with a standard extracellular contrast agent (gadobutrol) in vivo in a rat model of hepatic colorectal cancer metastases and in vitro by relaxometry measurements.
  
  
  METHODS
  Ten rats with hepatic colorectal cancer metastases were examined using a 9.4 T animal scanner (Bruker, Germany). Each animal was subjected to 2 contrast-enhanced magnetic resonance imaging experiments separated by 2 days receiving 0.1 mmol/kg body weight gadobutrol and 0.1 mmol/kg body weight P03277 intravenously in a random manner. T1-weighted self-gated fast low-angle shot sequences (time to repetition/time to echo, 45/2.5 milliseconds; flip angle, 45 degrees; acquisition time, 1:23 minutes; voxel size, 0.2 × 0.2 × 1.0 mm) were acquired before and at 10 consecutive time points after contrast injection. We assessed signal-to-noise ratio (SNR) of tumor (SNRtumor) and normal liver tissue (SNRliver), contrast-to-noise ratio, and lesion enhancement (LE). In addition, relaxation rates of P03277 and gadobutrol were assessed in vitro in human plasma at 37°C at a field strength of 9.4 T.Statistical analyses included paired t tests and Wilcoxon matched pairs signed rank tests.
  
  
  RESULTS
  SNRliver, SNRtumor, contrast-to-noise ratio, and LE were significantly higher (P < 0.05) using P03277 for all time points as compared with gadobutrol. Both agents demonstrated comparable contrast kinetics with an early peak enhancement immediately after application (initial percent LE: gadobutrol, 84%; P03277, 156%) and an early and continuous washout during the examination period (final percent LE: gadobutrol, 36%; P03277, 63%). In vitro evaluation of relaxivities demonstrated markedly higher R1 for P03277 (8.6 mM s) as compared with gadobutrol (4.2 mM s).
  
  
  CONCLUSIONS
  This study provides the first in vivo and in vitro data of P03277, an experimental extracellular MR contrast agent. P03277 demonstrates significantly better enhancement properties as compared with gadobutrol in experimental hepatic colorectal cancer metastases. In addition, in vitro data demonstrate superior relaxivities of P03277 at a broad spectrum of different field strengths. Hence, this new agent has the potential to improve lesion conspicuity and subsequently sensitivity in diagnostic imaging for both clinical magnetic resonance imaging at 1.5 or 3 T and ultra-high field applications between 4.7 and 9.4 T.
authors.affiliation: From the *Clinic of Diagnostic and Interventional Radiology, Saarland University Medical Center, Homburg, Germany; †Guerbet Research, Aulnay-sous-Bois, France; and ‡Institute for Clinical and Experimental Surgery, Saarland University Medical Center, Homburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Fries
authors.forename: Andres
authors.initials: A
authors.lastname: Müller
authors.forename: Roland
authors.initials: R
authors.lastname: Seidel
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.forename: Gero
authors.initials: G
authors.lastname: Denda
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Günther
authors.initials: G
authors.lastname: Schneider
authors.forename: Arno
authors.initials: A
authors.lastname: Buecker
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology; D003287:Contrast Media; D056831:Coordination Complexes; D004195:Disease Models, Animal; D005260:Female; D005682:Gadolinium; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000556:secondary; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009942:Organometallic Compounds; D011856:Radiographic Image Enhancement; D051381:Rats
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D009942:Organometallic Compounds; C090600:gadobutrol; D005682:Gadolinium