Abstract BS3-2: Molecular Imaging of Breast Cancer: Visualizing In Vivo Breast Cancer Biology

Author(s):  
DA Mankoff ◽  
LA Chodosh
2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Qingqing Meng ◽  
Zheng Li

Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular eventsin vivo.Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained.


2004 ◽  
Vol 11 (2) ◽  
pp. 179-189 ◽  
Author(s):  
P E L√∏nning

The development of aromatase inhibitors for breast cancer therapy is a result of successful translational research exploring the biochemical effects of different compounds in vivo. Studies assessing plasma oestrogen levels as well as in vivo aromatase inhibition have revealed a consistent difference with respect to biochemical efficacy between the third generation compounds (anastrozole, letrozole and exemestane) and the previous, first and second generation drugs, corresponding to the improved clinical effects of these compounds as outlined in large phase III studies. Thus, endocrine evaluation has been found to be a valid surrogate parameter for clinical efficacy. Moreover, the results from these studies have added important biological information to our understanding of endocrine regulation of breast cancer. Based on the clinical results so far, aromatase inhibitors are believed to play a key role in future adjuvant therapy of postmenopausal breast cancer patients and potentially also for breast cancer prevention. Interesting findings such as the lack of cross-resistance between steroidal and non-steroidal compounds should be further explored, as this may add additional information to our understanding of breast cancer biology.


2009 ◽  
Vol 6 (12) ◽  
pp. an4-an5
Author(s):  
Seth T Gammon ◽  
Warren M Leevy ◽  
Merrill Loechner

2018 ◽  
Vol 26 (5-6) ◽  
pp. 145-156 ◽  
Author(s):  
Darshini Kuruppu ◽  
Deepak Bhere ◽  
Christian T. Farrar ◽  
Khalid Shah ◽  
Anna-Liisa Brownell ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
M. F. Fiordelisi ◽  
L. Auletta ◽  
L. Meomartino ◽  
L. Basso ◽  
G. Fatone ◽  
...  

Precision and personalized medicine is gaining importance in modern clinical medicine, as it aims to improve diagnostic precision and to reduce consequent therapeutic failures. In this regard, prior to use in human trials, animal models can help evaluate novel imaging approaches and therapeutic strategies and can help discover new biomarkers. Breast cancer is the most common malignancy in women worldwide, accounting for 25% of cases of all cancers and is responsible for approximately 500,000 deaths per year. Thus, it is important to identify accurate biomarkers for precise stratification of affected patients and for early detection of responsiveness to the selected therapeutic protocol. This review aims to summarize the latest advancements in preclinical molecular imaging in breast cancer mouse models. Positron emission tomography (PET) imaging remains one of the most common preclinical techniques used to evaluate biomarker expression in vivo, whereas magnetic resonance imaging (MRI), particularly diffusion-weighted (DW) sequences, has been demonstrated as capable of distinguishing responders from nonresponders for both conventional and innovative chemo- and immune-therapies with high sensitivity and in a noninvasive manner. The ability to customize therapies is desirable, as this will enable early detection of diseases and tailoring of treatments to individual patient profiles. Animal models remain irreplaceable in the effort to understand the molecular mechanisms and patterns of oncologic diseases.


2009 ◽  
Vol 106 (17) ◽  
pp. 7022-7027 ◽  
Author(s):  
Min Wu ◽  
Lina Jung ◽  
Adrian B. Cooper ◽  
Christina Fleet ◽  
Lihao Chen ◽  
...  

Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results in uncontrolled growth in a permissive microenvironment. Accordingly, physiologically relevant models of human breast cancer that recapitulate these events are needed to study cancer biology and evaluate therapeutic agents. Here, we report the generation and utilization of the human breast cancer in mouse (HIM) model, which is composed of genetically engineered primary human breast epithelial organoids and activated human breast stromal cells. By using this approach, we have defined key genetic events required to drive the development of human preneoplastic lesions as well as invasive adenocarcinomas that are histologically similar to those in patients. Tumor development in the HIM model proceeds through defined histological stages of hyperplasia, DCIS to invasive carcinoma. Moreover, HIM tumors display characteristic responses to targeted therapies, such as HER2 inhibitors, further validating the utility of these models in preclinical compound testing. The HIM model is an experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies.


2009 ◽  
Vol 02 (04) ◽  
pp. 343-352
Author(s):  
CHAO-WEI CHEN ◽  
TIFFANY R. BLACKWELL ◽  
RENEE NAPHAS ◽  
PAUL T. WINNARD ◽  
VENU RAMAN ◽  
...  

Fluorescence molecular imaging enables the visualization of basic molecular processes such as gene expression, enzyme activity, and disease-specific molecular interactions in vivo using targeted contrast agents, and therefore, is being developed for early detection and in situ characterization of breast cancers. Recent advances in developing near-infrared fluorescent imaging contrast agents have enabled the specific labeling of human breast cancer cells in mouse model systems. In synergy with contrast agent development, this paper describes a needle-based fluorescence molecular imaging device that has the strong potential to be translated into clinical breast biopsy procedures. This microendoscopy probe is based on a gradient-index (GRIN) lens interfaced with a laser scanning microscope. Specifications of the imaging performance, including the field-of-view, transverse resolution, and focus tracking characteristics were calibrated. Orthotopic MDA-MB-231 breast cancer xenografts stably expressing the tdTomato red fluorescent protein (RFP) were used to detect the tumor cells in this tumor model as a proof of principle study. With further development, this technology, in conjunction with the development of clinically applicable, injectable fluorescent molecular imaging agents, promises to perform fluorescence molecular imaging of breast cancers in vivo for breast biopsy guidance.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Hanyi Fang ◽  
Mengting Li ◽  
Qingyao Liu ◽  
Yongkang Gai ◽  
Lujie Yuan ◽  
...  

AbstractTriple-negative breast cancer (TNBC) is a subtype of breast cancer in which the estrogen receptor and progesterone receptor are not expressed, and human epidermal growth factor receptor 2 is not amplified or overexpressed either, which make the clinical diagnosis and treatment very challenging. Molecular imaging can provide an effective way to diagnose TNBC. Upconversion nanoparticles (UCNPs), are a promising new generation of molecular imaging probes. However, UCNPs still need to be improved for tumor-targeting ability and biocompatibility. This study describes a novel probe based on cancer cell membrane-coated upconversion nanoparticles (CCm-UCNPs), owing to the low immunogenicity and homologous-targeting ability of cancer cell membranes, and modified multifunctional UCNPs. This probe exhibits excellent performance in breast cancer molecular classification and TNBC diagnosis through UCL/MRI/PET tri-modality imaging in vivo. By using this probe, MDA-MB-231 was successfully differentiated between MCF-7 tumor models in vivo. Based on the tumor imaging and molecular classification results, the probe is also expected to be modified for drug delivery in the future, contributing to the treatment of TNBC. The combination of nanoparticles with biomimetic cell membranes has the potential for multiple clinical applications.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dengfeng Li ◽  
Chengyan Dong ◽  
Xiaohong Ma ◽  
Xinming Zhao

Abstract Background The motif RXDLXXL-based nanoprobes allow specific imaging of integrin αvβ6, a protein overexpressed during tumorigenesis and tumor progression of various tumors. We applied a novel RXDLXXL-coupled cyclic arginine-glycine-aspartate (RGD) nonapeptide conjugated with ultrasmall superparamagnetic iron oxide nanoparticles (referred to as cFK-9-USPIO) for the application of integrin αvβ6-targeted magnetic resonance (MR) molecular imaging for breast cancer. Methods A novel MR-targeted nanoprobe, cFK-9-USPIO, was synthesized by conjugating integrin αvβ6-targeted peptide cFK-9 to N-amino (−NH2)-modified USPIO nanoparticles via a dehydration esterification reaction. Integrin αvβ6-positive mouse breast cancer (4 T1) and integrin αvβ6 negative human embryonic kidney 293 (HEK293) cell lines were incubated with cFK-9-AbFlour 647 (blocking group) or cFK-9-USPIO (experimental group), and subsequently imaged using laser scanning confocal microscopy (LSCM) and 3.0 Tesla magnetic resonance imaging (MRI) system. The affinity of cFK-9 targeting αvβ6 was analyzed by calculating the mean fluorescent intensity in cells, and the nanoparticle targeting effect was measured by the reduction of T2 values in an in vitro MRI. The in vivo MRI capability of cFK-9-USPIO was investigated in 4 T1 xenograft mouse models. Binding of the targeted nanoparticles to αvβ6-positive 4 T1 tumors was determined by ex vivo histopathology. Results In vitro laser scanning confocal microscopy (LSCM) imaging showed that the difference in fluorescence intensity between the targeting and blocking groups of 4 T1 cells was significantly greater than that in HEK293 cells (P < 0.05). The in vitro MRI demonstrated a more remarkable T2 reduction in 4 T1 cells than in HEK293 cells (P < 0.001). The in vivo MRI of 4 T1 xenograft tumor-bearing nude mice showed significant T2 reduction in tumors compared to controls. Prussian blue staining further confirmed that αvβ6 integrin-targeted nanoparticles were specifically accumulated in 4 T1 tumors and notably fewer nanoparticles were detected in 4 T1 tumors of mice injected with control USPIO and HEK293 tumors of mice administered cFK-9-USPIO. Conclusions Integrin αvβ6-targeted nanoparticles have great potential for use in the detection of αvβ6-overexpressed breast cancer with MR molecular imaging.


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