[11C]Choline-PET imaging of breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1110-1110
Author(s):  
L. M. Kenny ◽  
R. C. Coombes ◽  
K. Contractor ◽  
J. Stebbing ◽  
A. Al-Nahhas ◽  
...  

1110 Background: Molecular imaging techniques are increasingly being used in cancer diagnosis, staging, and assessment of response to treatment. This study sought to evaluate, for the first time, [11C]choline-PET in patients with breast cancer. The potential of [11C]choline-PET for differentiating tumours from normal tissue, correlation with molecular markers, determine its normal variability range, and finally the effect of trastuzumab on [11C]choline uptake in patients with breast cancer was investigated. Methods: 21 patients with newly diagnosed and recurrent breast cancer AJCC stage II-IV were enrolled in the study, all of whom had a baseline dynamic [11C]choline-PET scan with arterial sampling. 14 patients had 2 [11C]choline-PET scans to examine reproducibility, and 7 had a scan after trastuzumab. Analysis of [11C]choline uptake was measured using SUV, Ki (irreversible retention), and IRF@60min (retention using spectral analysis). Results: Breast tumour lesions were visualised by [11C]choline PET in all patients. The difference in tumour and non-tumour uptake were significant for SUV, Ki, and IRF@60 min (Wilcoxon p < 0.0001 for all parameters). [11C]choline uptake was reproducible in breast tumour lesions (r2 = 0.945 for SUV, 0.894 for Ki, and 0.799 for IRF60). The metabolism analysis of arterial plasma samples in 19 patients showed that [11C]choline decreased rapidly post-injection such that at 60 mins the mean radioactivity in arterial plasma due to choline was 15.15 ± 2.16%.Early responses to trastuzumab were determined to be significant in 5 lesions which corresponded with 3 clinical responses. Conclusions: [11C]choline-PET is a promising imaging modality in breast cancer, and could play an important role for determining response to novel treatment strategies in vivo. No significant financial relationships to disclose.

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2348
Author(s):  
Leon Riehakainen ◽  
Chiara Cavallini ◽  
Paolo Armanetti ◽  
Daniele Panetta ◽  
Davide Caramella ◽  
...  

Non-invasive longitudinal imaging of osseointegration of bone implants is essential to ensure a comprehensive, physical and biochemical understanding of the processes related to a successful implant integration and its long-term clinical outcome. This study critically reviews the present imaging techniques that may play a role to assess the initial stability, bone quality and quantity, associated tissue remodelling dependent on implanted material, implantation site (surrounding tissues and placement depth), and biomarkers that may be targeted. An updated list of biodegradable implant materials that have been reported in the literature, from metal, polymer and ceramic categories, is provided with reference to the use of specific imaging modalities (computed tomography, positron emission tomography, ultrasound, photoacoustic and magnetic resonance imaging) suitable for longitudinal and non-invasive imaging in humans. The advantages and disadvantages of the single imaging modality are discussed with a special focus on preclinical imaging for biodegradable implant research. Indeed, the investigation of a new implant commonly requires histological examination, which is invasive and does not allow longitudinal studies, thus requiring a large number of animals for preclinical testing. For this reason, an update of the multimodal and multi-parametric imaging capabilities will be here presented with a specific focus on modern biomaterial research.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jae Heon Kim ◽  
Hong J. Lee ◽  
Yun Seob Song

A reliablein vivoimaging method to localize transplanted cells and monitor their viability would enable a systematic investigation of cell therapy. Most stem cell transplantation studies have used immunohistological staining, which does not provide information about the migration of transplanted cellsin vivoin the same host. Molecular imaging visualizes targeted cells in a living host, which enables determining the biological processes occurring in transplanted stem cells. Molecular imaging with labeled nanoparticles provides the opportunity to monitor transplanted cells noninvasively without sacrifice and to repeatedly evaluate them. Among several molecular imaging techniques, magnetic resonance imaging (MRI) provides high resolution and sensitivity of transplanted cells. MRI is a powerful noninvasive imaging modality with excellent image resolution for studying cellular dynamics. Several types of nanoparticles including superparamagnetic iron oxide nanoparticles and magnetic nanoparticles have been used to magnetically label stem cells and monitor viability by MRI in the urologic field. This review focuses on the current role and limitations of MRI with labeled nanoparticles for tracking transplanted stem cells in urology.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Praachi B. Jain ◽  
Patrícia S. Guerreiro ◽  
Sara Canato ◽  
Florence Janody

AbstractAberrant expression of the Spectraplakin Dystonin (DST) has been observed in various cancers, including those of the breast. However, little is known about its role in carcinogenesis. In this report, we demonstrate that Dystonin is a candidate tumour suppressor in breast cancer and provide an underlying molecular mechanism. We show that in MCF10A cells, Dystonin is necessary to restrain cell growth, anchorage-independent growth, self-renewal properties and resistance to doxorubicin. Strikingly, while Dystonin maintains focal adhesion integrity, promotes cell spreading and cell-substratum adhesion, it prevents Zyxin accumulation, stabilizes LATS and restricts YAP activation. Moreover, treating DST-depleted MCF10A cells with the YAP inhibitor Verteporfin prevents their growth. In vivo, the Drosophila Dystonin Short stop also restricts tissue growth by limiting Yorkie activity. As the two Dystonin isoforms BPAG1eA and BPAG1e are necessary to inhibit the acquisition of transformed features and are both downregulated in breast tumour samples and in MCF10A cells with conditional induction of the Src proto-oncogene, they could function as the predominant Dystonin tumour suppressor variants in breast epithelial cells. Thus, their loss could deem as promising prognostic biomarkers for breast cancer.


2012 ◽  
Vol 35 (3) ◽  
pp. 129-143 ◽  
Author(s):  
Woonggyu Jung ◽  
Stephen A. Boppart

In pathology, histological examination of the “gold standard” to diagnose various diseases. It has contributed significantly toward identifying the abnormalities in tissues and cells, but has inherent drawbacks when used for fast and accurate diagnosis. These limitations include the lack ofin vivoobservation in real time and sampling errors due to limited number and area coverage of tissue sections. Its diagnostic yield also varies depending on the ability of the physician and the effectiveness of any image guidance technique that may be used for tissue screening during excisional biopsy. In order to overcome these current limitations of histology-based diagnostics, there are significant needs for either complementary or alternative imaging techniques which perform non-destructive, high resolution, and rapid tissue screening. Optical coherence tomography (OCT) is an emerging imaging modality which allows real-time cross-sectional imaging with high resolutions that approach those of histology. OCT could be a very promising technique which has the potential to be used as an adjunct to histological tissue observation when it is not practical to take specimens for histological processing, when large areas of tissue need investigating, or when rapid microscopic imaging is needed. This review will describe the use of OCT as an image guidance tool for fast tissue screening and directed histological tissue sectioning in pathology.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2918
Author(s):  
Simone Borgoni ◽  
Emre Sofyalı ◽  
Maryam Soleimani ◽  
Heike Wilhelm ◽  
Karin Müller-Decker ◽  
...  

Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, depending on the degree of severity of the disease at diagnosis, 10 to 40% of these tumors eventually relapse due to resistance development. Even though recent novel approaches as the combination with CDK4/6 inhibitors increased the overall survival of relapsing patients, this remains relatively short and there is a urgent need to find alternative targetable pathways. In this study we profiled the early phases of the resistance development process to uncover drivers of this phenomenon. Time-resolved analysis revealed that ATF3, a member of the ATF/CREB family of transcription factors, acts as a novel regulator of the response to therapy via rewiring of central signaling processes towards the adaptation to endocrine treatment. ATF3 was found to be essential in controlling crucial processes such as proliferation, cell cycle, and apoptosis during the early response to treatment through the regulation of MAPK/AKT signaling pathways. Its essential role was confirmed in vivo in a mouse model, and elevated expression of ATF3 was verified in patient datasets, adding clinical relevance to our findings. This study proposes ATF3 as a novel mediator of endocrine resistance development in breast cancer and elucidates its role in the regulation of downstream pathways activities.


2011 ◽  
Vol 57 (1) ◽  
pp. 18-32 ◽  
Author(s):  
Claire Corcoran ◽  
Anne M Friel ◽  
Michael J Duffy ◽  
John Crown ◽  
Lorraine O'Driscoll

BACKGROUND Successful treatment of breast cancer is enhanced by early detection and, if possible, subsequent patient-tailored therapy. Toward this goal, it is essential to identify and understand the most relevant panels of biomarkers, some of which may also have relevance as therapeutic targets. METHODS We critically reviewed published literature on microRNAs (miRNAs) as relevant to breast cancer. SUMMARY Since the initial recognition of the association of miRNAs with breast cancer in 2005, studies involving cell lines, in vivo models, and clinical specimens have implicated several functions for miRNAs, including suppressing oncogenesis and tumors, promoting or inhibiting metastasis, and increasing sensitivity or resistance to chemotherapy and targeted agents in breast cancer. For example, miR-21 is overexpressed in both male and female breast tumors compared with normal breast tissue and has been associated with advanced stage, lymph node positivity, and reduced survival time. miR-21 knock-down in cell-line models has been associated with increased sensitivity to topotecan and taxol in vitro and the limitation of lung metastasis in vivo. Furthermore, the discovery of extracellular miRNAs (including miR-21), existing either freely or in exosomes in the systemic circulation, has led to the possibility that such molecules may serve as biomarkers for ongoing patient monitoring. Although additional investigations are necessary to fully exploit the use of miRNAs in breast cancer, there is increasing evidence that miRNAs have potential not only to facilitate the determination of diagnosis and prognosis and the prediction of response to treatment, but also to act as therapeutic targets and replacement therapies.


Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1696
Author(s):  
Angelos Karlas ◽  
Antonio Nunes ◽  
Wouter Driessen ◽  
Evangelos Liapis ◽  
Josefine Reber

Breast cancer is a complex tumor type involving many biological processes. Most chemotherapeutic agents exert their antitumoral effects by rapid induction of apoptosis. Another main feature of breast cancer is hypoxia, which may drive malignant progression and confer resistance to various forms of therapy. Thus, multi-aspect imaging of both tumor apoptosis and oxygenation in vivo would be of enormous value for the effective evaluation of therapy response. Herein, we demonstrate the capability of a hybrid imaging modality known as multispectral optoacoustic tomography (MSOT) to provide high-resolution, simultaneous imaging of tumor apoptosis and oxygenation, based on both the exogenous contrast of an apoptosis-targeting dye and the endogenous contrast of hemoglobin. MSOT imaging was applied on mice bearing orthotopic 4T1 breast tumors before and following treatment with doxorubicin. Apoptosis was monitored over time by imaging the distribution of xPLORE-APOFL750©, a highly sensitive poly-caspase binding apoptotic probe, within the tumors. Oxygenation was monitored by tracking the distribution of oxy- and deoxygenated hemoglobin within the same tumor areas. Doxorubicin treatment induced an increase in apoptosis-depending optoacoustic signal of xPLORE-APOFL750© at 24 h after treatment. Furthermore, our results showed spatial correspondence between xPLORE-APO750© and deoxygenated hemoglobin. In vivo apoptotic status of the tumor tissue was independently verified by ex vivo fluorescence analysis. Overall, our results provide a rationale for the use of MSOT as an effective tool for simultaneously investigating various aspects of tumor pathophysiology and potential effects of therapeutic regimes based on both endogenous and exogenous molecular contrasts.


Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 157
Author(s):  
Henry J. Thompson ◽  
Elizabeth S. Neil ◽  
John N. McGinley ◽  
Vanessa K. Fitzgerald ◽  
Karam El Bayoumy ◽  
...  

In vivo evidence of heterogeneous effects of n-3 fatty acids (N3FA) on cell signaling pathways associated with the reduced growth of breast cancer has been reported and is consistent with the expectation that N3FA will not exert uniform effects on all molecular subtypes of the disease. Similarly, available evidence indicates that many metabolites of N3FA are synthesized by mammalian cells and that they exert metabolite-specific biological activities. To begin to unravel the complex relationships among molecular subtypes and effects exerted by specific N3FA metabolites on those pathways, proof-of-concept experiments were conducted using cell lines representative of common molecular subtypes of human breast cancer. N3FA differed in anticancer activity with docosahexaenoic acid (DHA) having greater anticancer activity than eicosapentaenoic acid. 4-oxo-docosahexaenoic (4-oxo-DHA), a penultimate metabolite of 5-lipoxygenase mediated DHA metabolism, induced dose-dependent inhibition of cell number accumulation with apoptosis as a primary effector mechanism. Interrogation of protein expression data using the Ingenuity Pathway Analysis (IPA) bioinformatics platform indicated that 4-oxo-DHA differentially impacted six canonical pathways and the cellular functions they regulate across common molecular subtypes of breast cancer. This included the endocannabinoid pathway for cancer inhibition that has not been previously reported. These findings provide a rationale for juxtaposing molecular subtype targeted treatment strategies with the adjuvant use of specific N3FA metabolites as an example of precision onco-nutrition (PON) for the management and control of breast cancer.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vasiliki Mallikourti ◽  
Sai Man Cheung ◽  
Tanja Gagliardi ◽  
Nicholas Senn ◽  
Yazan Masannat ◽  
...  

AbstractLipid composition in breast cancer, a central marker of disease progression, can be non-invasively quantified using 2D MRS method of double quantum filtered correlation spectroscopy (DQF-COSY). The low signal to noise ratio (SNR), arising from signal retention of only 25% and depleted lipids within tumour, demands improvement approaches beyond signal averaging for clinically viable applications. We therefore adapted and examined combination algorithms, designed for 1D MRS, for 2D MRS with both internal and external references. Lipid composition spectra were acquired from 17 breast tumour specimens, 15 healthy female volunteers and 25 patients with breast cancer on a clinical 3 T MRI scanner. Whitened singular value decomposition (WSVD) with internal reference yielded maximal SNR with an improvement of 53.3% (40.3–106.9%) in specimens, 84.4 ± 40.6% in volunteers, 96.9 ± 54.2% in peritumoural adipose tissue and 52.4% (25.1–108.0%) in tumours in vivo. Non-uniformity, as variance of improvement across peaks, was low at 21.1% (13.7–28.1%) in specimens, 5.5% (4.2–7.2%) in volunteers, 6.1% (5.0–9.0%) in peritumoural tissue, and 20.7% (17.4–31.7%) in tumours in vivo. The bias (slope) in improvement ranged from − 1.08 to 0.21%/ppm along the diagonal directions. WSVD is therefore the optimal algorithm for lipid composition spectra with highest SNR uniformly across peaks, reducing acquisition time by up to 70% in patients, enabling clinical applications.


2012 ◽  
Vol 35 (5-6) ◽  
pp. 317-337 ◽  
Author(s):  
Yasaman Ardeshirpour ◽  
Amir H. Gandjbakhche ◽  
Laleh Najafizadeh

In vivooptical imaging is being conducted in a variety of medical applications, including optical breast cancer imaging, functional brain imaging, endoscopy, exercise medicine, and monitoring the photodynamic therapy and progress of neoadjuvant chemotherapy. In the past three decades,in vivodiffuse optical breast cancer imaging has shown promising results in cancer detection, and monitoring the progress of neoadjuvant chemotherapy. The use of near infrared spectroscopy for functional brain imaging has been growing rapidly. In fluorescence imaging, the difference between autofluorescence of cancer lesions compared to normal tissues were used in endoscopy to distinguish malignant lesions from normal tissue or inflammation and in determining the boarders of cancer lesions in surgery. Recent advances in drugs targeting specific tumor receptors, such as AntiBodies (MAB), has created a new demand for developing non-invasivein vivoimaging techniques for detection of cancer biomarkers, and for monitoring their down regulations during therapy. Targeted treatments, combined with new imaging techniques, are expected to potentially result in new imaging and treatment paradigms in cancer therapy. Similar approaches can potentially be applied for the characterization of other disease-related biomarkers. In this chapter, we provide a review of diffuse optical and fluorescence imaging techniques with their application in functional brain imaging and cancer diagnosis.


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