title: Evaluation of gadolinium 2,5-BPA-DO3A, a new macrocyclic hepatobiliary chelate, in normal liver and metastatic disease on high field magnetic resonance imaging.
abstract: OBJECTIVE
  A new hepatobiliary gadolinium chelate, gadolinium (Gd) 2,5-BPA-DO3A, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved extracellular contrast agent, and Gd Cy2-DOTA, a second hepatobiliary chelate in preclinical development. The ligand in Gd 2,5-BPA-DO3A is macrocyclic in nature, as opposed to the linear structure of Gd DTPA. Gadolinium 2,5-BPA-DO3A was evaluated on magnetic resonance imaging at 1.5 T, examining specifically liver parenchymal enhancement and lesion delineation, the latter in metastatic disease.
  
  
  METHODS
  Gadolinium 2,5-BPA-DO3A was evaluated in five normal rhesus monkeys and four New Zealand White rabbits with implanted VX-2 liver tumors. These studies were compared with magnetic resonance exams in the same animals using Gd HP-DO3A and Gd Cy2-DOTA. A contrast dose of 0.1 mmol/kg intravenous was employed in each instance, with the sequence of administration (for the three agents) randomized and at least 72 hours between injections. Spin echo breathhold T1-weighted scans were obtained before and at multiple times after contrast administration. Postcontrast scans were acquired from 1 to 60 minutes after injection in the monkeys and from 1 to 240 minutes in the rabbits.
  
  
  RESULTS
  Enhancement of normal liver parenchyma was markedly superior with Gd 2,5-BPA-DO3A compared with Gd HP-DO3A and Gd Cy2-DOTA in both monkeys and rabbits. At 2 and 60 minutes after contrast administration, the liver signal intensity in the monkey was 452 +/- 56 and 440 +/- 69 with Gd 2,5-BPA-DO3A compared with 295 +/- 34 and 256 +/- 38 with Gd HP-DO3A. The difference between agents was statistically significant at all postcontrast time points in the rhesus monkey. Excretion of contrast into the gall bladder was consistently observed after Gd 2,5-BPA-DO3A injection in both animal species. Maximum lesion conspicuity occurred in the rabbit at 45 minutes after Gd 2,5-BPA-DO3A administration. At 45 minutes postinjection, liver-lesion contrast was 0.60 +/- 0.15 with Gd 2,5-BPA-DO3A, 0.35 +/- 0.11 with Gd Cy2-DOTA, and 0.12 +/- 0.04 with Gd HP-DO3A, with the differences between agents being statistically significant.
  
  
  CONCLUSIONS
  Gadolinium 2,5-BPA-DO3A is superior to both Gd Cy2-DOTA and Gd HP-DO3A in the degree of enhancement of normal liver parenchyma achieved after intravenous injection. This leads to improved liver lesion delineation with Gd 2,5-BPA-DO3A on delayed postcontrast magnetic resonance scans.
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: D000818:Animals; D002277:Carcinoma / Q000175:diagnosis / Q000473:pathology / Q000556:secondary; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics; D005682:Gadolinium / Q000008:administration & dosage / Q000493:pharmacokinetics; D005704:Gallbladder / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D007089:Image Enhancement; D007275:Injections, Intravenous; D008099:Liver / Q000033:anatomy & histology*; D008114:Liver Neoplasms, Experimental / Q000175:diagnosis* / Q000473:pathology / Q000556:secondary*; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D011817:Rabbits; D013997:Time Factors
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C103343:gadolinium 2,5-BPA-DO3A; C094044:gadolinium Cy(2)DOTA; C062402:gadoteridol; D005682:Gadolinium