Clinical production, stability studies and PET imaging with 16-alpha-[18F]fluoroestradiol ([18F]FES) in ER positive breast cancer patients.

Abstract

PURPOSE:

18F-Fluoroestradiol [18F]FES has emerged as a valuable PET tracer to predict the response to hormone therapy in recurrent or metastatic breast cancer patients. A clinically acceptable product requires a rapid reliable synthesis and must be demonstrated to maintain chemical stability and receptor specific uptake during patient studies. [18F]FES then becomes a dependable tracer for the evaluation and management of breast cancer patients.

METHODS:

An improved automated radiosynthesis of [18F]FES was developed. Stability studies of the injectible form of [18F]FES were performed up to 24 h after dose formulation under normal storage conditions. A comparative FES/FDG PET imaging in ER+ breast cancer patients is reported.

RESULTS:

The improved synthesis procedure utilizes fewer hydrolysis steps and a single high performance liquid column chromatography (HPLC) purification of the labeled mixture affording [18F]FES in good yield with high radiochemical purity (>99%). Stability studies with purified [18F]FES in saline/ethanol (85:15 v/v) indicated no radiolytic or chemical degradation of this radiopharmaceutical when stored for 24 h at 20-24 degrees C. Positron Emission Tomography (PET) studies with [18F]FES and [18F]FDG in estrogen receptor positive (ER+) breast cancer patients indicated that while FDG accumulation was seen in all metabolically hyperactive sites, the uptake of FES clearly delineated the ER+ tissues regions.

CONCLUSIONS:

An improved automated synthesis of [18F]FES has been developed and the integrity of this product has been validated by long term stability studies and clinical PET imaging studies in ER+ breast cancer patients. A lack of concordance between FES and FDG uptake in a patient with metastatic breast cancer suggests specificity of the FES for tumors expressing estrogen receptors.

• Authors: Piyush Kumar, John Mercer, Courtney Doerkson, Katia Tonkin, Alexander J B McEwan
• Journal: Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques (J Pharm Pharm Sci) Vol. 10 Issue 2 Pg. 256s-265s ( 2007) ISSN: 1482-1826 [Electronic] Canada
• PMID: 17718929 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorine Radioisotopes
• Receptors, Estrogen
• Estradiol
• 16-fluoroestradiol

Topics

• Automation
• Breast Neoplasms (diagnostic imaging)
• Chromatography, High Pressure Liquid
• Drug Stability
• Drug Storage
• Estradiol (analogs & derivatives, chemical synthesis)
• Female
• Fluorine Radioisotopes
• Humans
• Neoplasm Metastasis
• Positron-Emission Tomography
• Receptors, Estrogen (metabolism)
• Sensitivity and Specificity