ZR-75-1 breast cancer models to study the utility of 18F-FES by PET imaging

Abstract

Background: Breast cancer is a hormone-dependent tumor, and 70-80% of breast cancer patients are estrogen receptor (ER) positive. ZR-75-1 cell lines are more consistent with human breast cancer, which is mostly ER positive and PR positive. To better study the biological characteristics of 18 F-fluoroestradiol ( 18 F-FES) in breast cancer patients, ZR-75-1 breast cancer models were selected to provide a basis for further clinical application.Methods: 18 F-FES uptake in vivo was evaluated in ZR-75-1 tumor-bearing mice, using MCF-7 tumorbearing mice as a positive control. Competitive inhibition experiment was also performed, using ER downregulator fulvestrant. Biodistribution of 18 F-FES was observed in ZR-75-1 breast tumor-bearing mice scanning by 18 F-FES-PET/CT in vivo and γ counter ex vivo. The expression of ER was also determined by immunohistochemistry. An abnormal toxicity test was performed in ICR male mice whose behavior and vital signs were observed within 48 hours of 18 F-FES injection. OLINDA/EXM 2.0 software was used to calculate the absorbed doses of adult female body phantoms.Results: There was no significant difference in FES uptake between ZR-75-1 and MCF-7 tumor-bearing mice. Intervention with fulvestrant decreased the uptake of 18 F-FES. Biodistribution studies demonstrated that the uptake of 18 F-FES was high in the liver and kidneys but low in the brain. Other than excretory organs, the uptake of 18 F-FES in ER-positive breast tumors was significantly higher than in ER-negative tissues. The estimated human effective dose was 0.016 mSv/MBq for the adult female body model. Conclusions:The 18 F-FES tracer could have suitable properties for imaging ER-positive breast tumors. It may provide an important evidence for individualized treatment of patients with breast cancer.

How Shilajit-Based Nanocarriers Alter Classical Doxorubicin Delivery to Breast Cancer Cells (MCF-7 and ZR-75-1)

“…In contrast, MCF-7 cells are estrogen-positive but progesteronereceptor-negative. 30 As shown in Figure 6, the cell viability of ZR-75-1 cells after 24 h treatment with SHN-Dox was significantly higher than that after Dox treatment in low doses (3.7, 7.5, and 15 μg/mL). At high doses of 30, 60, and 120 μg/mL, the cell viability of ZR-75-1 cells was lower than in the Dox-treated group, but the difference was not significant.…”

“…ZR-75-1 cells, which are mostly estrogen- and progesterone-positive, are more representative of human breast cancer. In contrast, MCF-7 cells are estrogen-positive but progesterone-receptor-negative . As shown in Figure , the cell viability of ZR-75-1 cells after 24 h treatment with SHN-Dox was significantly higher than that after Dox treatment in low doses (3.7, 7.5, and 15 μg/mL).…”

Development of Radiopharmaceuticals for NPY Receptor-5 (Y5) Nuclear Imaging in Tumors by Synthesis of Specific Agonists and Investigation of Their Binding Mode

“…31 Therefore, given the ER-independence of Y 5 and the higher Y 5 expression in human breast cancer cells compared to normal breast tissues (contrary to the Y 1 ), 7 we were interested in developing a radiopharmaceutical targeting the Y 5 capable of delivering diagnostic and therapeutic radiations. Importantly, when considering biodistribution data, [ 68 Ga]Ga-DOTA-sY 5 ago performed equally well or even better in imaging MCF-7 tumors than published data for [ 18 F]-FES 32 with, however, several specific advantages. First, [ 68 Ga]Ga-DOTA-sY 5 ago showed lower hepato-biliary excretion and lower uptake in the gall bladder, 32 making PET images clearer; second, uptake of [ 68 Ga]Ga-DOTA-sY 5 ago in ER-positive normal organs such as the ovary is low or even absent (0.40 ± 0.12 %ID/g; yielding a tumor/ovary ratio of almost 7) contrary to [ 18 F]-FES (ovary uptake was 3.1 ± 0.7 %ID/g at 30 min 33 ); third, DOTA-sY5ago holds the unique possibility for targeted radionuclide therapy.…”

“…Importantly, when considering biodistribution data, [ 68 Ga]Ga-DOTA-sY 5 ago performed equally well or even better in imaging MCF-7 tumors than published data for [ 18 F]-FES 32 with, however, several specific advantages. First, [ 68 Ga]Ga-DOTA-sY 5 ago showed lower hepato-biliary excretion and lower uptake in the gall bladder, 32 making PET images clearer; second, uptake of [ 68 Ga]Ga-DOTA-sY 5 ago in ER-positive normal organs such as the ovary is low or even absent (0.40 ± 0.12 %ID/g; yielding a tumor/ovary ratio of almost 7) contrary to [ 18 F]-FES (ovary uptake was 3.1 ± 0.7 %ID/g at 30 min 33 ); third, DOTA-sY5ago holds the unique possibility for targeted radionuclide therapy. Indeed, the DOTA macrocycle allows to arm sY5ago with therapeutic emitters such as 177 Lu, 225 Ac, or 161 Tb, making the treatment of metastatic ER-breast cancer possible when metastases show high uptake on PET imaging.…”

“…Fulllength peptides are commonly used to target the NPY system (Figure 1). To target Y 5 , some selective peptides have been identified in the past, including Ala 31 ,Aib 32 -NPY, 9 NPY, 10 and [cPP(1-7),NPY(19-23),Ala 31 ,Aib 32 ,Gln 34 ]hPP. 11 The later, referred to as sY 5 ago in this work, had proven especially potent at the Y 5 receptor and highly selective due to the Ala-Aib moiety, which drastically reduces activity at other NPY receptors.…”