4,4,16-Trifluoropalmitate: Design, Synthesis, Tritiation, Radiofluorination and Preclinical PET Imaging Studies on Myocardial Fatty Acid Oxidation.
ChemMedChem
; 15(23): 2317-2331, 2020 12 03.
Article
in En
| MEDLINE
| ID: mdl-32856369
ABSTRACT
Fatty acid oxidation (FAO) produces most of the ATP used to sustain the cardiac contractile work, although glycolysis is a secondary source of ATP under normal physiological conditions. FAO impairment has been reported in the advanced stages of heart failure (HF) and is strongly linked to disease progression and severity. Thus, from a clinical perspective, FAO dysregulation provides prognostic value for HF progression, the assessment of which could be used to improve patient monitoring and the effectiveness of therapy. Positron emission tomography (PET) imaging represents a powerful tool for the assessment and quantification of metabolic pathways inâ
vivo. Several FAO PET tracers have been reported in the literature, but none of them is in routine clinical use yet. Metabolically trapped tracers are particularly interesting because they undergo FAO to generate a radioactive metabolite that is subsequently trapped in the mitochondria, thus providing a quantitative means of measuring FAO inâ
vivo. Herein, we describe the design, synthesis, tritium labelling and radiofluorination of 4,4,16-trifluoro-palmitate (1) as a novel potential metabolically trapped FAO tracer. Preliminary PET-CT studies on [18 F]1 in rats showed rapid blood clearance, good metabolic stability - confirmed by using [3 H]1 in vitro - and resistance towards defluorination. However, cardiac uptake in rats was modest (0.24±0.04 % ID/g), and kinetic analysis showed reversible uptake, thus indicating that [18 F]1 is not irreversibly trapped.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Design
/
Radiopharmaceuticals
/
Fatty Acids
/
Positron Emission Tomography Computed Tomography
/
Myocardium
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
ChemMedChem
Journal subject:
FARMACOLOGIA
/
QUIMICA
Year:
2020
Type:
Article
Affiliation country:
United kingdom