Sensitivity and Isoform Specificity of 18 F-Fluorofuranylnorprogesterone for Measuring Progesterone Receptor Protein Response to Estradiol Challenge in Breast Cancer

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Kelley SalemAmy M Fowler

Abstract

The purpose of this study was to evaluate the ability of 21-18F-fluoro-16α,17α-[(R)-(1'-α-furylmethylidene)dioxy]-19-norpregn-4-ene-3,20-dione (18F-FFNP) to measure alterations in progesterone receptor (PR) protein level and isoform expression in response to estradiol challenge. Methods: T47D human breast cancer cells and female mice-bearing T47D tumor xenografts were treated with 17β-estradiol (E2) to increase PR expression. 18F-FFNP uptake was measured using cell uptake and tissue biodistribution assays. MDA-MB-231 breast cancer clonal cell lines were generated that express the A or B isoforms of human PR. PR protein levels, transcriptional function, and subcellular localization were determined. In vitro 18F-FFNP binding was measured via saturation and competitive binding curves. In vivo 18F-FFNP uptake was measured using tumor xenografts and positron emission tomography. Statistical significance was determined using analysis of variance and t-tests. Results: After 48 and 72 h of E2, 18F-FFNP uptake in T47D cells was maximally increased compared to both vehicle and 24 h E2 treatment (p<0.0001 vs ethanol; P = 0.02 and P = 0.0002 vs 24 h for 48 and 72 h, respectively). T47D tumor xenografts in mice treated with 72 h E2 had maxi...Continue Reading

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Citations

Jul 3, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Falguni BasuliRolf E Swenson
Jan 17, 2020·Hormones & Cancer·Amy M FowlerAparna M Mahajan
Aug 30, 2020·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Manoj KumarAmy M Fowler
Apr 28, 2021·Journal of Medicinal Chemistry·Yuta Takamura, Hiroki Kakuta
Mar 10, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Manoj KumarAmy M Fowler
Nov 17, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Manoj KumarAmy M Fowler
Nov 23, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Michel Paquette, Eric Turcotte

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