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In vivo quantification of ER-β expression by pharmacokinetic modeling: Studies with (18)F-FHNP PET

Antunes, I. F., Willemsen, A. T. M., Sijbesma, J. W. A., Boerema, A. S., van Waarde, A., Glaudemans, A. W. J. M., Dierckx, R. A., de Vries, E. G. E., Hospers, G. A. P. & de Vries, E. 13-Jul-2017 In : Journal of Nuclear Medicine.

Research output: Scientific - peer-reviewArticle

The estrogen receptor (ER) is a target for endocrine therapy in breast cancer patients. Individual quantification of ERα and ERβ expression, rather than total ER levels, might enable better prediction of the response to treatment. We recently developed the tracer 2-(18)F-fluoro-6-(6-hydroxynaphthalen-2-yl)pyridin-3-ol ((18)F-FHNP) for assessment of ERβ levels with positron emission tomography (PET). Here we investigated several pharmacokinetic analysis methods to quantify changes in ERβ availability with (18)F-FHNP-PET. Methods: Male nude rats were subcutaneously inoculated in the shoulder with ERα/ERβ-expressing SKOV3 human ovarian cancer cells. Two weeks after tumor inoculation, a dynamic (18)F-FHNP-PET scan with arterial blood sampling was acquired in rats treated with vehicle or various concentrations of estradiol (non-specific ER agonist) or genistein (ERβ selective agonist). Different pharmacokinetic models were applied to quantify ERβ availability in the tumor. Results: Irreversible uptake compartment models fitted the kinetics of (18)F-FHNP uptake better than reversible models. The irreversible 3-tissue compartment model, which included both the parent and the metabolite input function, gave comparable results as the irreversible 2-tissue compartment model with only a parent input function, indicating that radioactive metabolites contributed little to the tumor uptake. Patlak graphical analysis gave comparable metabolic rates (Ki) as compartment modeling. The Ki values correlated well with ERβ expression, but not with ERα, confirming that Ki is a suitable parameter to quantify ERβ expression. Standardized uptake values at 60 minutes after tracer injection also correlated (r2=0.47; P = 0.04) with ERβ expression. A reduction in (18)F-FHNP tumor uptake and Ki values was observed in the presence of estradiol or genistein. Conclusion:(18)F-FHNP-PET enables assessment of ERβ availability in tumor-bearing rats. The most suitable parameter to quantify ERβ expression is the Ki. However, a simplified static imaging protocol for determining the SUV can be applied to assess ERβ levels, if somewhat lower accuracy is acceptable.

Original languageEnglish
JournalJournal of Nuclear Medicine
StateE-pub ahead of print - 13-Jul-2017

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  • Journal Article

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