title: Comparison of gadolinium Cy2DOTA, a new hepatobiliary agent, and gadolinium HP-DO3A, an extracellular agent, in healthy liver and metastatic disease.
abstract: OBJECTIVE
  A new gadolinium (Gd) chelate with preferential hepatobiliary uptake, Gd Cy2DOTA, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved contrast agent with extracellular distribution. Liver enhancement was evaluated for these two contrast agents using magnetic resonance imaging, whereas an experimental model of metastatic disease was used to evaluate the agents' efficacy for liver-lesion delineation.
  
  
  METHODS
  The two agents were compared in four healthy Rhesus monkeys (eight studies) and five New Zealand White rabbits with implanted VX-2 liver tumors (ten studies). The contrast dose was 0.1 mmol/kg, with the agents given in random order and at least 72 hours between contrast injections. Breathhold T1-weighted spin echo scans were obtained at 1.5 tesla (T) before and after contrast was administered. Postcontrast scans were obtained 1 to 90 minutes after injection in the monkeys and 1 to 240 minutes after injection in the rabbits.
  
  
  RESULTS
  Prolonged hepatic enhancement, superior in degree to that with Gd HP-DO3A, was noted in both monkeys and rabbits after injection of Gd Cy2DOTA. Two minutes after contrast, liver SI was 1.94 +/- 0.05 with Gd Cy2DOTA compared with 1.51 +/- 0.05 with Gd HP-DO3A in monkeys. Sixty minutes after contrast, liver SI was 1.60 +/- 0.09 compared with 1.20 +/- 0.02. The difference between agents was significant at all times from 2 to 60 minutes after contrast injection (P < 0.01). Excretion of contrast into the gall bladder was observed in both animal species with Gd Cy2DOTA but not with Gd HP-DO3A. The maximum improvement in lesion conspicuity (rabbit) occurred 45 minutes after injection of Gd Cy2DOTA and 5 minutes after injection of Gd HP-DO3A. Sixty minutes after injection, liver-lesion contrast was 246 +/- 61 with Gd Cy2DOTA and 106 +/- 28 with Gd HP-DO3A, with a significant difference (P < 0.02).
  
  
  CONCLUSIONS
  Gd Cy2DOTA provides greater enhancement of the liver parenchyma on immediate and delayed magnetic resonance scans than does Gd HP-DO3A. On delayed scans, Gd Cy2DOTA provides superior delineation of metastatic liver lesions.
authors.affiliation: Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington 40536, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Runge
authors.forename: J W
authors.initials: JW
authors.lastname: Wells
authors.forename: N M
authors.initials: NM
authors.lastname: Williams
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000556:secondary*; D000818:Animals; D001659:Biliary Tract / Q000033:anatomy & histology*; D003287:Contrast Media / Q000008:administration & dosage; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005682:Gadolinium / Q000008:administration & dosage; D006571:Heterocyclic Compounds / Q000008:administration & dosage; D008099:Liver / Q000033:anatomy & histology*; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000556:secondary*; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D009942:Organometallic Compounds / Q000008:administration & dosage; D011817:Rabbits; D013997:Time Factors
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C094044:gadolinium Cy(2)DOTA; C062402:gadoteridol; D005682:Gadolinium