Assessment of the Novel Estrogen Receptor PET Tracer 4-Fluoro-11 beta-methoxy-16 alpha-[F-18]fluoroestradiol (4FMFES) by PET Imaging in a Breast Cancer Murine Model

作者：Paquette Michel; Phoenix Serge; Ouellet Rene; Langlois Rejean; van Lier Johan E; Turcotte Eric E; Benard Francois; Lecomte Roger^*

来源：Molecular Imaging and Biology, 2013, 15(5): 625-632.

DOI：10.1007/s11307-013-0638-7

• Receptor imaging
• Estrogen receptor alpha
• Breast cancer
• Knockdown tumor model
• Small animal PET

The aim of this study was to compare the in vivo stability, uptake, and positron emission tomography (PET) imaging performance of a novel estrogen receptor PET tracer, 4-fluoro-11 beta-methoxy-16 alpha-[F-18]fluoroestradiol (4FMFES), with 16 alpha-[F-18]fluoroestradiol (FES).
MC7-L1 and MC4-L2 (ER+) cell lines and their ER alpha-knockdown variants (ER alpha KD) were implanted subcutaneously in Balb/c mice. After 21 days, mice were imaged using either FES or 4FMFES. One hour post-injection, static images were acquired for 30 min and the tumor %ID/g uptake values were derived. Biodistribution data were also obtained 1 h following the injection of either FES or 4FMFES. Blood samples were taken at different times and analyzed on thin-layer chromatography to quantify the presence of radiometabolites for each radiotracer. To assess specific targeting to the estrogen receptors, mice bearing only ER+ tumors were treated with the competitive ER inhibitor fulvestrant 48 h prior to imaging with 4FMFES.
Metabolic stability was found to be similar for both tracers in mice. Both FES and 4FMFES differentiated ER+ tumors from ER alpha KD tumors in biodistribution and PET imaging studies. 4FMFES achieved a significantly higher %ID/g uptake in ER+ tumors and MC4-L2 ER alpha KD tumors than FES in the PET imaging studies. Also, tumor-to-background ratio was higher in ER+ tumors using 4FMFES compared to FES. Dissection data showed a significantly higher %ID/g in all tested cell lines and ER-rich tissues using 4FMFES versus FES. Fulvestrant-treated mice had either low or undetectable tumor uptake.
In a tumor-bearing mouse model, 4FMFES achieves better specific tumor uptake and better contrast than FES, making it a promising candidate for ER imaging.

• 出版日期2013-10