scholarly journals Study of the automated synthesis of the radiopharmaceutical fluoroestradiol-18F

2021 ◽  
Vol 9 (3) ◽  
Author(s):  
Luiza Mascarenhas Balieiro ◽  
Henrique Barcellos de Oliveira ◽  
Luiz Felipe Teixeira Silva ◽  
Maria Helena Bellini ◽  
Margareth Mie Nakamura Matsuda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Solid Phase ◽  
Metastatic Breast ◽  
Tumor Model ◽  
Radiochemical Yield ◽  
Automated Synthesis ◽  
Non Invasive ◽  
Biodistribution Studies ◽  
Estrogen Receptor Positive

Approximately 75% of breast cancer cells express estrogen receptor positive, being the second leading cause of cancer death among women worldwide with an incidence of 25% per year. 16α-[18F]-fluoro-17β-estradiol, FES-18F, is a radiopharmaceutical that binds to estrogen receptors enabling the acquisition of molecular images for non-invasive diagnosis of primary and metastatic breast cancer using PET-CT. The objective of this work was to study the synthesis of FES-18F in the GE TRACERlab® MXFDG module, using the chemical kit and the ABX® disposable cassette, and to determine the process yield and the analytical parameters to be used in the routine production of this radiopharmaceutical. Automated synthesis occurs in 75 minutes and includes percolation of [18F-] fluoride into an anion exchange cartridge, cartridge elution, 3-step azeotropic drying, labeling using precursor 3-methoxymethyl-16β,17β-epiestriol-O-cyclic sulfone (MMSE) and a hydrolysis step. Product purification is done in the module using solid phase extraction (SPE) cartridges. The radiochemical yield was reproductive, regardless of fluor-18 activity at entry into the module, and the results of quality control tests suggest that the radiopharmaceutical meets the criteria established for other fluor-18-labelled radiopharmaceuticals that have monographs in official compendiums. In vivo biodistribution studies in healthy animals and with a tumor model developed with MCF-7 cells, demonstrated radiopharmaceutical uptake in excretory organs and specificity for breast tumor cells.

68Ga-labeled HBED-CC Variant of uPAR Targeting Peptide AE105 Compared with 68Ga-NODAGA-AE105

2019 ◽  
Vol 18 (9) ◽  
pp. 1289-1294 ◽  
Author(s):  
Kusum Vats ◽  
Rohit Sharma ◽  
Haladhar D. Sarma ◽  
Drishty Satpati ◽  
Ashutosh Dash
Keyword(s):  
Solid Phase ◽  
Evaluation Studies ◽  
Radiochemical Yield ◽  
In Vivo Evaluation ◽  
Peptide Conjugates ◽  
Biodistribution Studies ◽  
Target Organs ◽  
U87mg Tumor

Aims: The urokinase Plasminogen Activator Receptors (uPAR) over-expressed on tumor cells and their invasive microenvironment are clinically significant molecular targets for cancer research. uPARexpressing cancerous lesions can be suitably identified and their progression can be monitored with radiolabeled uPAR targeted imaging probes. Hence this study aimed at preparing and evaluating two 68Ga-labeled AE105 peptide conjugates, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 as uPAR PET-probes. Method: The peptide conjugates, HBED-CC-AE105-NH2 and NODAGA-AE105-NH2 were manually synthesized by standard Fmoc solid phase strategy and subsequently radiolabeled with 68Ga eluted from a commercial 68Ge/68Ga generator. In vitro cell studies for the two radiotracers were performed with uPAR positive U87MG cells. Biodistribution studies were carried out in mouse xenografts with the subcutaneously induced U87MG tumor. Results: The two radiotracers, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 that were prepared in >95% radiochemical yield and >96% radiochemical purity, exhibited excellent in vitro stability. In vivo evaluation studies revealed higher uptake of 68Ga-HBED-CC-AE105 in U87MG tumor as compared to 68Ga-NODAGAAE105; however, increased lipophilicity of 68Ga-HBED-CC-AE105 resulted in slower clearance from blood and other non-target organs. The uPAR specificity of the two radiotracers was ascertained by significant (p<0.05) reduction in the tumor uptake with a co-injected blocking dose of unlabeled AE-105 peptide. Conclusion: Amongst the two radiotracers studied, the neutral 68Ga-NODAGA-AE105 with more hydrophilic chelator exhibited faster clearance from non-target organs. The conjugation of HBED-CC chelator (less hydrophilic) resulted in negatively charged 68Ga-HBED-CC-AE105 which was observed to have high retention in blood that decreased target to non-target ratios.

scholarly journals Low Intensity Focused Ultrasound Augmented Multifunctional Nanoparticles for Integrating Ultrasound Imaging and Synergistic Therapy of Metastatic Breast Cancer

2021 ◽  
Author(s):  
Qian Zhang ◽  
Wen Wang ◽  
Hongyuan Shen ◽  
Hongyu Tao ◽  
Yating Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ultrasound Imaging ◽  
Focused Ultrasound ◽  
Metastatic Breast ◽  
Sonodynamic Therapy ◽  
Non Invasive ◽  
Low Intensity ◽  
Negative Effect

Abstract The metastasis of breast cancer is believed to have a negative effect on its prognosis. Benefiting from the remarkable deep-penetrating and non-invasive characteristics, sonodynamic therapy (SDT) demonstrates a whole series of potential leading to cancer treatment. To relieve the limitation of monotherapy, a multifunctional nanoplatform has been explored to realize the synergistic treatment efficiency. Herein, we establish a novel multifunctional nano-system which encapsulates chlorin e6 (Ce6, for SDT), perfluoropentane (PFP, for ultrasound imaging), and docetaxel (DTX, for chemotherapy) in a well-designed PLGA core-shell structure. The synergistic nanoparticle (CPDP NPs) featured with excellent biocompatibility and stability primarily enables its further application. Upon low intensity focused ultrasound (LIFU) irradiation, the enhanced ultrasound imaging could be revealed both in vitro and in vivo. More importantly, combined with LIFU, the nanoparticle exhibits intriguing antitumor capability through Ce6 induced cytotoxic reactive oxygen species as well as DTX releasing to generate a concerted therapeutic efficiency. Furthermore, this treating strategy actives a strong anti-metastasis capability by which lung metastatic nodules have been significantly reduced. The results indicate that the SDT-oriented nanoplatform combined with chemotherapy could be provided as a promising approach in elevating effective synergistic therapy and suppressing lung metastasis of breast cancer.

Non-invasive immunoPET imaging of PD-L1 using anti-PD-L1-B11 in breast cancer and melanoma tumor model

2021 ◽  
Author(s):  
Aditya Bansal ◽  
Mukesh K. Pandey ◽  
Whitney Barham ◽  
Xin Liu ◽  
Susan M. Harrington ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Model ◽  
Melanoma Tumor ◽  
Non Invasive

scholarly journals Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jingjing Yang ◽  
Yulu Zhou ◽  
Shuduo Xie ◽  
Ji Wang ◽  
Zhaoqing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Morphological Changes ◽  
Tumor Model ◽  
Independent Manner ◽  
Regulated Cell Death ◽  
Anti Cancer ◽  
Cancer Agent ◽  
Approved Drugs

Abstract Background Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxidation and is involved in various pathophysiological conditions, including cancer. Targeting ferroptosis is considered to be a novel anti-cancer strategy. The identification of FDA-approved drugs as ferroptosis inducers is proposed to be a new promising approach for cancer treatment. Despite a growing body of evidence indicating the potential efficacy of the anti-diabetic metformin as an anti-cancer agent, the exact mechanism underlying this efficacy has not yet been fully elucidated. Methods The UFMylation of SLC7A11 is detected by immunoprecipitation and the expression of UFM1 and SLC7A11 in tumor tissues was detected by immunohistochemical staining. The level of ferroptosis is determined by the level of free iron, total/lipid Ros and GSH in the cells and the morphological changes of mitochondria are observed by transmission electron microscope. The mechanism in vivo was verified by in situ implantation tumor model in nude mice. Results Metformin induces ferroptosis in an AMPK-independent manner to suppress tumor growth. Mechanistically, we demonstrate that metformin increases the intracellular Fe2+ and lipid ROS levels. Specifically, metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, metformin combined with sulfasalazine, the system xc− inhibitor, can work in a synergistic manner to induce ferroptosis and inhibit the proliferation of breast cancer cells. Conclusions This study is the first to demonstrate that the ability of metformin to induce ferroptosis may be a novel mechanism underlying its anti-cancer effect. In addition, we identified SLC7A11 as a new UFMylation substrate and found that targeting the UFM1/SLC7A11 pathway could be a promising cancer treatment strategy.

scholarly journals Osteoblast-Derived Paracrine and Juxtacrine Signals Protect Disseminated Breast Cancer Cells from Stress

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1366
Author(s):  
Russell Hughes ◽  
Xinyue Chen ◽  
Natasha Cowley ◽  
Penelope D. Ottewell ◽  
Rhoda J. Hawkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Accessory Cell ◽  
Cancer Cell Survival

Metastatic breast cancer in bone is incurable and there is an urgent need to develop new therapeutic approaches to improve survival. Key to this is understanding the mechanisms governing cancer cell survival and growth in bone, which involves interplay between malignant and accessory cell types. Here, we performed a cellular and molecular comparison of the bone microenvironment in mouse models representing either metastatic indolence or growth, to identify mechanisms regulating cancer cell survival and fate. In vivo, we show that regardless of their fate, breast cancer cells in bone occupy niches rich in osteoblastic cells. As the number of osteoblasts in bone declines, so does the ability to sustain large numbers of breast cancer cells and support metastatic outgrowth. In vitro, osteoblasts protected breast cancer cells from death induced by cell stress and signaling via gap junctions was found to provide important juxtacrine protective mechanisms between osteoblasts and both MDA-MB-231 (TNBC) and MCF7 (ER+) breast cancer cells. Combined with mathematical modelling, these findings indicate that the fate of DTCs is not controlled through the association with specific vessel subtypes. Instead, numbers of osteoblasts dictate availability of protective niches which breast cancer cells can colonize prior to stimulation of metastatic outgrowth.

scholarly journals Enhanced Survival with Implantable Scaffolds That Capture Metastatic Breast Cancer Cells In Vivo

2016 ◽  
Vol 76 (18) ◽  
pp. 5209-5218 ◽  
Author(s):  
Shreyas S. Rao ◽  
Grace G. Bushnell ◽  
Samira M. Azarin ◽  
Graham Spicer ◽  
Brian A. Aguado ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Breast

Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer

2016 ◽  
Vol 34 (25) ◽  
pp. 2961-2968 ◽  
Author(s):  
Charlotte Fribbens ◽  
Ben O’Leary ◽  
Lucy Kilburn ◽  
Sarah Hrebien ◽  
Isaac Garcia-Murillas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Phase Iii ◽  
Wild Type ◽  
Estrogen Receptor Positive ◽  
Esr1 Mutations ◽  
The Impact

Purpose ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.

scholarly journals Practice-Changing Interventions in the Systemic Management of Breast Cancer

2020 ◽  
Vol 18 (7.5) ◽  
pp. 941-944
Author(s):  
William J. Gradishar
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Subtype ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Targeted Agents ◽  
Her2 Positive ◽  
Nccn Guidelines ◽  
Estrogen Receptor Positive ◽  
Treatment Paradigm

Systemic treatment for metastatic breast cancer now incorporates many targeted agents and a plethora of combinations specific to the breast cancer subtype. New to the treatment paradigm are fam-trastuzumab deruxtecan-nxki, and tucatinib for HER2-positive disease; the PI3K inhibitor alpelisib in combination with fulvestrant for estrogen receptor–positive and PIK3CA-mutated tumors; PARP inhibitors for patients with germline BRCA1/2 mutations; and the anti–PD-L1 agent atezolizumab in combination with albumin-bound paclitaxel for triple-negative disease with PD-L1 mutations in tumors. In addition, for estrogen receptor–positive disease, the role of CDK4/6 inhibitors increased substantially during the past year, as overall survival results have emerged. These targeted agents are greatly improving patient outcomes, and thus have all been incorporated into the NCCN Guidelines for Breast Cancer.

scholarly journals IMMUNOLOGICAL IMBALANCE IN BREAST CANCER AND LUNG CANCER IN POSTMENOPAUSAL WOMEN

2018 ◽  
Vol 20 (6) ◽  
pp. 927-934 ◽  
Author(s):  
A. N. Glushkov ◽  
E. G. Polenok ◽  
L. A. Gordeeva ◽  
S. A. Mun ◽  
M. V. Kostyanko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Postmenopausal Women ◽  
Marked Effect ◽  
Solid Phase ◽  
Anticancer Effect ◽  
Class A ◽  
Solid Phase Immunoassay ◽  
The One

Previous studies reported some associations between class A antibodies specific for benzo[a]pyrene (IgA-Bp), estradiol (IgA-Es) and progesterone (IgA-Pg) and breast cancer (BC) in women like as with lung cancer (LC) in men. It was suggested that IgA-Bp and IgA-Es may stimulate tumor initiation and promotion, whereas IgA-Pg may inhibit the in vivo human carcinogenesis.The purpose of this study was to identify the suggested associations of such immunological imbalance with BC and LC in postmenopausal women.The serum A-class antibodies specific to benzo[a]pyrene, estradiol and progesterone (IgA-Bp, IgA-Es, IgA- Pg) were studied in 335 healthy women, 824 breast cancer (BC) patients and 127 cases of lung cancer (LC) by means of non-competitive solid phase immunoassay. The following results were obtained: Increased ratio of IgA-Bp and IgA-Es amounts exceeding the IgA-Pg levels was associated with a higher risk of breast cancer (OR = 2.8 and 2.4 respectively, p < 0.0001), and higher risk of LC (OR = 2.9 and 2.8, respectively, p < 0.0001). Conversely, the OR values decreased to 0.3-0.4 for BC and LC if IgA-Pg levels were higher than IgA-Bp and IgA-Es levels (p < 0.0001). These findings confirm the hypothesis that IgA-Bp and IgA-Es are capable to stimulate, and IgA-Pg, to inhibit the BC and LC occurrence n postmenopausal women. The balance between IgA-Bp and IgA-Es, on the one hand, and IgA-Pg, on the other hand, is much more important than individual contents of these antibodies.In conclusion, the phenomenon of “immunological interference” is revealed, i.e., the mutual enhancement of IgA-Bp and IgA-Es effects, thus, probably, stimulating the initial and subsequent events of carcinogenesis initiation and promotion, with a weak anticancer effect of IgA-Pg, and by weakening the mutual procarcinogenic effects of IgA-Bp and IgA-Es by the marked effect of IgA-Pg.

Sign in / Sign up

Export Citation Format

Share Document