Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

Frank I Lin; E M Gonzalez; S Kummar; K Do; J Shih; S Adler; K A Kurdziel; A Ton; B Turkbey; P M Jacobs; S Bhattacharyya; A P Chen; J M Collins; J H Doroshow; P L Choyke; M L Lindenberg

doi:10.1007/s00259-016-3561-8

Utility of ¹⁸F-fluoroestradiol (¹⁸F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

Eur J Nucl Med Mol Imaging. 2017 Mar;44(3):500-508. doi: 10.1007/s00259-016-3561-8. Epub 2016 Nov 21.

Authors

Frank I Lin^{1

2}, E M Gonzalez³, S Kummar⁴, K Do⁴, J Shih⁵, S Adler⁶, K A Kurdziel³, A Ton³, B Turkbey³, P M Jacobs⁷, S Bhattacharyya⁸, A P Chen⁹, J M Collins⁴, J H Doroshow⁴, P L Choyke³, M L Lindenberg³

Affiliations

¹ Cancer Imaging Program, National Cancer Institute, NIH, Bethesda, MD, USA. frank.lin2@nih.gov.
² Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA. frank.lin2@nih.gov.
³ Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
⁴ Division of Cancer Treatment and Diagnosis and Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
⁵ Biometric Research Program, National Cancer Institute, NIH, Bethesda, MD, USA.
⁶ Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, MD, 21702, USA.
⁷ Cancer Imaging Program, National Cancer Institute, NIH, Bethesda, MD, USA.
⁸ Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA.
⁹ Early Clinical Trials Development Program, DCTD, National Cancer Institute, Bethesda, MD, USA.

Abstract

Background: Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. ¹⁸F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes ¹⁸F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen.

Methods: Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with ¹⁸F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with ¹⁸F-FES 1-5 days post administration of Z-endoxifen.

Results: Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration.

Conclusion: F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

Keywords: 18F-FES; Fluoroestradiol; Pharmacodynamic marker; Positron emission tomography (PET); Z-endoxifen.

Publication types

Clinical Trial

MeSH terms

Adult
Aged
Breast Neoplasms / diagnostic imaging*
Breast Neoplasms / drug therapy
Breast Neoplasms / genetics
Breast Neoplasms, Male / diagnostic imaging*
Breast Neoplasms, Male / drug therapy
Breast Neoplasms, Male / genetics
Estradiol / analogs & derivatives*
Estrogen Antagonists / therapeutic use
Female
Genital Neoplasms, Female / diagnostic imaging*
Genital Neoplasms, Female / drug therapy
Genital Neoplasms, Female / genetics
Humans
Male
Middle Aged
Positron Emission Tomography Computed Tomography*
Radiopharmaceuticals*
Receptors, Estrogen / antagonists & inhibitors
Receptors, Estrogen / genetics
Tamoxifen / analogs & derivatives
Tamoxifen / therapeutic use

Substances

Estrogen Antagonists
Radiopharmaceuticals
Receptors, Estrogen
Tamoxifen
4-hydroxy-N-desmethyltamoxifen
Estradiol
16-fluoroestradiol

Abstract

Publication types

MeSH terms

Substances

Grants and funding