| Hepatobiliary delivery of polyaminopolycarboxylate chelates: synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate. | |
| | |
MedLine Citation:
|
PMID: 1907855 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance. |
| | |
Authors:
|
D A Betebenner; P L Carney; A M Zimmer; J M Kazikiewicz; E Brücher; A D Sherry; D K Johnson |
Related Documents
:
|
23172595 - α-hydroxy-β-keto acid rearrangement-decarboxylation: impact on thiamine diphosphate-d... 23295935 - Prevalent polymorphisms in wild-type hiv-1 integrase are unlikely to engender drug resi... 17933475 - Theoretical and experimental vibrational study of miconazole and its dimers with organi... 3553465 - Evaluation of the renal clearance of technetium-99m pahida in dogs. 7748315 - Hyperexcitability in adrenal cells after culture in ethanol: withdrawal or excitotoxicity. 12926915 - Identification of metabolites of (-)-epicatechin gallate and their metabolic fate in th... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Bioconjugate chemistry Volume: 2 ISSN: 1043-1802 ISO Abbreviation: Bioconjug. Chem. Publication Date: 1991 Mar-Apr |
Date Detail:
|
Created Date: 1991-09-19 Completed Date: 1991-09-19 Revised Date: 2003-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 9010319 Medline TA: Bioconjug Chem Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 117-23 Citation Subset: IM |
Affiliation:
|
Abbott Laboratories, Department 90M, Abbott Park, Illinois 60064. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Biliary Tract / metabolism*, radionuclide imaging Chelating Agents / metabolism* Cholic Acids / chemical synthesis, pharmacokinetics* Edetic Acid / chemical synthesis, pharmacokinetics*, pharmacology Female Indium Radioisotopes / diagnostic use Isotope Labeling Liver / metabolism*, radionuclide imaging Mice Mice, Inbred BALB C Potentiometry Rabbits Thermodynamics Tissue Distribution |
| Chemical | |
Reg. No./Substance:
|
0/Chelating Agents; 0/Cholic Acids; 0/Indium Radioisotopes; 132910-41-9/N-carboxymethyl)-N-(2-(bis(carboxymethyl)amino)ethyl)-3-(4-(N'-(2-((3,7,12-trihydroxycholan-24-oyl)amino)ethyl)(thioureido)phenyl)alanine; 60-00-4/Edetic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Reengineering the catalytic lysine of aspartate aminotransferase by chemical elaboration of a geneti...
Next Document: Multicentre evaluation of the blood gas-electrolyte-analyser "BGE".