title: In vivo (1)H MRS and (31)P MRSI of the response to cyclocreatine in transgenic mouse liver expressing creatine kinase.
abstract: Hepatocyte transplantation has been explored as a therapeutic alternative to liver transplantation, but a means to monitor the success of the procedure is lacking. Published findings support the use of in vivo (31)P MRSI of creatine kinase (CK)-expressing hepatocytes to monitor proliferation of implanted hepatocytes. Phosphocreatine tissue level depends upon creatine (Cr) input to the CK enzyme reaction, but Cr measurement by (1)H MRS suffers from low signal-to-noise ratio (SNR). We examine the possibility of using the Cr analog cyclocreatine (CCr, a substrate for CK), which is quickly phosphorylated to phosphocyclocreatine (PCCr), as a higher SNR alternative to Cr. (1)H MRS and (31)P MRSI were employed to measure the effect of incremental supplementation of CCr upon PCCr, γ-ATP, pH and Pi /ATP in the liver of transgenic mice expressing the BB isoform of CK (CKBB) in hepatocytes. Water supplementation with 0.1% CCr led to a peak total PCCr level of 17.15 ± 1.07 mmol/kg wet weight by 6 weeks, while adding 1.0% CCr led to a stable PCCr liver level of 18.12 ± 3.91 mmol/kg by the fourth day of feeding. PCCr was positively correlated with CCr, and ATP concentration and pH declined with increasing PCCr. Feeding with 1% CCr in water induced an apparent saturated level of PCCr, suggesting that CCr quantization may not be necessary for quantifying expression of CK in mice. These findings support the possibility of using (31)P MRS to noninvasively monitor hepatocyte transplant success with CK-expressing hepatocytes.
authors.affiliation: Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Radiology, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Cui
authors.affiliation: Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Kamaiah
authors.initials: K
authors.lastname: Jayalakshmi
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Laibin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Chandan
authors.initials: C
authors.lastname: Guha
authors.affiliation: Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Radiology, Albert Einstein College of Medicine, Bronx, NY, USA.|Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Branch
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism*; D003404:Creatinine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005240:Feasibility Studies; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010759:Phosphorus Isotopes / Q000493:pharmacokinetics; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*
chemical_list: D010759:Phosphorus Isotopes; C012260:cyclocreatine; D000255:Adenosine Triphosphate; D003404:Creatinine; D003402:Creatine Kinase
keywords: MRS; creatine kinase; cyclocreatine; hepatocytes; mouse liver; phosphocyclocreatine; spectroscopic imaging