Synthesis and evaluation of the novel 2-[18F]fluoro-3-propoxy-triazole-pyridine-substituted losartan for imaging AT1 receptors
| Autor: | Ana C. Valdivia, Maryam Hachem, Basma Ismail, Natasha Arksey, Robert A. deKemp, Tayebeh Hadizad, Rob S. Beanlands, Jean N. DaSilva |
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| Rok vydání: | 2014 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Triazole Pharmaceutical Science 010402 general chemistry 01 natural sciences Biochemistry chemistry.chemical_compound Drug Discovery medicine Receptor Molecular Biology Kidney Angiotensin II receptor type 1 010405 organic chemistry Chemistry Organic Chemistry Angiotensin II 0104 chemical sciences 3. Good health Candesartan Losartan medicine.anatomical_structure Click chemistry Molecular Medicine medicine.drug Nuclear chemistry |
| Zdroj: | Bioorganic & Medicinal Chemistry. 22:3931-3937 |
| ISSN: | 0968-0896 |
| Popis: | The 2-[(18)F]fluoro-3-pent-4-yn-1-yloxypyridine ([(18)F]FPyKYNE) analog of the potent non-peptide angiotensin II type 1 receptor (AT1R) blocker losartan was produced via click chemistry linking [(18)F]FPyKYNE to azide-modified tetrazole-protected losartan followed by TFA deprotection. Preliminary small animal imaging with positron emission tomography (PET) in rats displayed high uptake in the kidneys with good contrast to surrounding tissue. Rat metabolism displayed the presence of 23% unchanged tracer in plasma at 30 min. Upon co-administration with AT₁R blocker candesartan (2.5, 5 and 10 mg/kg), a dose-dependent reduction (47-65%) in tracer uptake was observed in the kidney, while no difference was observed following AT₂R blocker PD123,319 (5 mg/kg), indicating binding selectivity for AT₁R over AT₂R and potential for imaging AT₁R using PET. |
| Databáze: | OpenAIRE |
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