title: Synthesis of a DOTA (Gd3+)-conjugate of proton-pump inhibitor pantoprazole for gastric wall imaging studies.
abstract: Magnetic resonance imaging (MRI) is used to evaluate gastrointestinal (GI) structure and functions in humans. Despite filling the viscus lumen with a contrast agent, visualization of the viscus wall is limited. To overcome this limitation, we de novo synthesized a conjugate that covalently combines a Gd-based MRI contrast agent, encaged with a chelating agent (DOTA), with pantoprazole, which is a widely used proton pump inhibitor that binds to proton pumps in the stomach and colon. The DOTA linkage was installed at a mechanism-based strategic location in the pantoprazole molecule to minimize a possible negative effect of the structural modification on the drug. It is anticipated that by defining the wall of the stomach and colon, this compound will facilitate functional MRI of the GI tract in humans.
authors.affiliation: Chemical Synthesis Core Facility, Mayo Clinic Jacksonville, FL 32224, USA. maharvi.ghulam@mayo.edu
authors.forename: Ghulam M
authors.initials: GM
authors.lastname: Maharvi
authors.forename: Adil E
authors.initials: AE
authors.lastname: Bharucha
authors.forename: Abdul H
authors.initials: AH
authors.lastname: Fauq
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000737:chemistry*; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000737:chemistry*; D011859:Radiography; D013270:Stomach / Q000000981:diagnostic imaging; D013696:Temperature
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D003287:Contrast Media; D056831:Coordination Complexes; D006573:Heterocyclic Compounds, 1-Ring; D054328:Proton Pump Inhibitors; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D005682:Gadolinium; D000077402:Pantoprazole; D000251:Adenosine Triphosphatases