Pedram Heidari MD, Presenter: Nothing to Disclose

Francis Deng BA, Abstract Co-Author: Nothing to Disclose

Shadi A. Esfahani MD, MPH, Abstract Co-Author: Nothing to Disclose

Alicia Leece, Abstract Co-Author: Nothing to Disclose

Umar Mahmood MD, PhD, Abstract Co-Author: Research Grant, Sabik Medical Inc

Fulvestrant, an estrogen receptor degrader, is now widely used in management of breast cancer (BrCa). Currently, there are no methods to optimize treatment dosing of fulvestrant. This study assesses the utility of pharmacodynamic imaging using 16α-[18F]-fluoroestradiol (18F-FES) in dose optimization of fulvestrant in a preclinical model of ER+ BrCa.

MCF7 cells (ER+) were incubated with different doses of fulvestrant for 24 h. Retention of 18F-FES was measured and compared to ERα protein expression (ELISA) and ESR1 mRNA transcription (qPCR). MCF7 tumors were grown in ovariectomized nude mice. The mice were randomly assigned to vehicle, low- (0.05mg), medium- (0.45mg) or high-dose (5mg) treatment groups (n=5-7). Two days after fulvestrant treatment, PET/CT was performed using 18F-FES and 18F-FDG. ER expression was assayed by immunohistochemistry (IHC), ELISA, and qPCR on xenografts. Tumor proliferation was assessed using Ki-67 IHC.

In vitro, fulvestrant was equipotent at reducing 18F-FES uptake as ER protein expression, despite stimulating mRNA transcription severalfold. In xenografts, ER expression significantly decreased with fulvestrant treatment in a dose-dependent manner both in ELISA of tumor lysates and IHC staining, despite similar mRNA expression. No difference in Ki-67 staining was observed among the treatment groups. We observed a significant dose-dependent reduction of 18F-FES PET SUVmean with fulvestrant treatment, but no significant difference among the treatment groups in 18F-FDG PET parameters.

We demonstrated that 18F-FES uptake mirrors the dose-dependent changes in functional ER expression with fulvestrant treatment which precedes the changes in tumor metabolism and proliferation. Pharmacodynamic imaging of estrogen receptor may be useful for tracking early efficacy of ER degradation and guiding ER-targeted therapy dosing in BrCa patients.

precise anti-ER dosing in individual patients using pharmacodynamic imaging of ER may improve therapy response

Heidari, P, Deng, F, Esfahani, S, Leece, A, Mahmood, U, Pharmacodynamic Imaging of Estrogen Receptor Guides Dosing of Fulvestrant.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14011757.html