MicroPET Imaging of Breast Cancer with a Dual-Targeted Molecular Probe 68Ga-RGD-BBN

2011 ◽  
Vol 27 (4) ◽  
pp. 335-344 ◽  
Author(s):  
Huiyun ZHAO ◽  
Yan LIU ◽  
Bing JIA ◽  
Fan WANG ◽  
Zhaofei LIU
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ragini Kothari ◽  
Veronica Jones ◽  
Dominique Mena ◽  
Viviana Bermúdez Reyes ◽  
Youkang Shon ◽  
...  

AbstractThis study addresses the core issue facing a surgical team during breast cancer surgery: quantitative prediction of tumor likelihood including estimates of prediction error. We have previously reported that a molecular probe, Laser Raman spectroscopy (LRS), can distinguish healthy and tumor tissue. We now report that combining LRS with two machine learning algorithms, unsupervised k-means and stochastic nonlinear neural networks (NN), provides rapid, quantitative, probabilistic tumor assessment with real-time error analysis. NNs were first trained on Raman spectra using human expert histopathology diagnostics as gold standard (74 spectra, 5 patients). K-means predictions using spectral data when compared to histopathology produced clustering models with 93.2–94.6% accuracy, 89.8–91.8% sensitivity, and 100% specificity. NNs trained on k-means predictions generated probabilities of correctness for the autonomous classification. Finally, the autonomous system characterized an extended dataset (203 spectra, 8 patients). Our results show that an increase in DNA|RNA signal intensity in the fingerprint region (600–1800 cm−1) and global loss of high wavenumber signal (2800–3200 cm−1) are particularly sensitive LRS warning signs of tumor. The stochastic nature of NNs made it possible to rapidly generate multiple models of target tissue classification and calculate the inherent error in the probabilistic estimates for each target.


2020 ◽  
Author(s):  
Yi Yang ◽  
Jun Zhang ◽  
Huifeng Zou ◽  
Yang Shen ◽  
Yiwei Wu

Abstract Introduction: Peptides containing the asparagine-glycine-arginine (NGR) sequence have been found to specifically bind to cluster of differentiation 13 (CD13) (aminopeptidase N), a tumor neovascular biomarker that is overexpressed on the surface of angiogenic blood vessels and various tumor cells and plays an important role in angiogenesis and tumor progression. The aim of this study was to evaluate the efficacy of a gallium-68 ( 68 Ga)-labeled dimeric cyclic NGR (cNGR) peptide as a new molecular probe that binds to CD13 in vitro and in vivo .Materials and Methods: A dimeric cNGR peptide conjugated with 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) and DOTA-c(NGR) 2 was synthesized and labeled with 68 Ga. In vitro uptake and binding analysis was performed in two ovarian tumor cell lines, ES2 and SKOV3, each of which have different expression levels of CD13. An in vivo biodistribution study was performed in normal mice, and micro positron emission tomography (PET) imaging was performed in nude mice xenografts with ES2 and SKOV3 tumors. Results : 68 Ga-DOTA-c(NGR) 2 with high radiochemical purity (>95%) was obtained and found to be stable at room temperature and when incubated with bovine serum at 37°C for 3 h. In vitro studies showed that uptake of 68 Ga-DOTA-c(NGR) 2 in ES2 cells increased over time, was higher than that in SKOV3 cells at all time points, and could be blocked by cold DOTA-c(NGR) 2 . Biodistribution studies demonstrated that 68 Ga-DOTA-c(NGR) 2 was mainly excreted from the kidney and rapidly cleared from blood. MicroPET imaging of ES2 tumor xenografts showed that focal uptake in tumors was distinctly observed from 1 to 1.5 h post-injection of 68 Ga-DOTA-c(NGR) 2 . Clear and high-contrast tumor visualization occurred at 1 h, which corresponded to the highest tumor/background ratio of 10.30±0.26. Moreover, accumulation of the probe in ES2 tumors apparently declined with pretreatment of unlabeled peptide, which further proved the specificity of 68 Ga-DOTA-c(NGR) 2 . In SKOV3 tumor models, the tumor was not obviously displayed under the same imaging protocols. Conclusion : We conclude that 68 Ga-DOTA-c(NGR) 2 might be a potential molecular probe for evaluating the expression levels of CD13 in different tumors, thereby providing a basis for targeting angiogenesis in cancer therapy.


2020 ◽  
Author(s):  
Xinyu Wang ◽  
Peng Xu ◽  
Yuying Jiao ◽  
Sha Luan ◽  
Yue Gao ◽  
...  

Abstract Background Murine double minute 2 (MDM2) is an oncogene that is important for tumorigenesis, tumor metastasis and chemotherapy resistance. We aimed to synthesize a molecular imaging probe, 99mTc-HYNIC-siRNA 1489, which could specifically bind to MDM2. The [99mTc]HYNIC-siRNA 1489 molecular probe provides an effective way to assess MDM2 expression via SPECT. Method: Three siRNAs were designed and their inhibitory efficiencies were tested using western blots and qRT-PCR. The selected siRNA was labeled with the radionuclide 99 m-technetium (99mTc) through the chelator HYNIC. The bioactivity and properties of [99mTc]HYNIC-siRNA 1489 were determined before mouse imaging. Imaging and the biodistribution of the probe were used to assess its targeting ability. Results SiRNA 1489, which was labeled with 99mTc, displayed a strong inhibitory effect in MCF-7 cell lines. The radiochemical purity of [99mTc]HYNIC-siRNA 1489 was stable at different temperatures in PBS and bovine serum. The T/M ratio of mice injected with [99mTc]HYNIC-siRNA 1489 was higher than that of those injected with the negative control, [99mTc]HYNIC-NC siRNA. The percentage injected dose per g (%ID/g) of the tumors injected with 99mTc-HYNIC-siRNA 1489 was greater than that of the control group. Conclusions The [99mTc]HYNIC-siRNA 1489 was taken up by the tumor, which had a high level of MDM2. The probe exhibited a sufficient retention time in the tumor. It might afford an effective strategy for evaluating MDM2 expression and achieving earlier diagnosis in breast cancer.


2019 ◽  
Vol 22 (3) ◽  
pp. 772-779 ◽  
Author(s):  
Haitao Zhao ◽  
Huannan Meng ◽  
Jun Wen ◽  
Cheng Wang ◽  
Jianjun Liu ◽  
...  

2013 ◽  
Vol 16 (2) ◽  
pp. 410-412 ◽  
Author(s):  
Sudesh T. Manjare ◽  
Sungsoo Kim ◽  
Won Do Heo ◽  
David G. Churchill

2004 ◽  
Vol 6 (5) ◽  
pp. 350-359 ◽  
Author(s):  
X CHEN ◽  
S LIU ◽  
Y HOU ◽  
M TOHME ◽  
R PARK ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-12
Author(s):  
Giang H. T. Au ◽  
Wan Y. Shih ◽  
Wei-Heng Shih ◽  
Linette Mejias ◽  
Vanlila K. Swami ◽  
...  

Positive margins have been a critical issue that hinders the success of breast- conserving surgery. The incidence of positive margins is estimated to range from 20% to as high as 60%. Currently, there is no effective intraoperative method for margin assessment. It would be desirable if there is a rapid and reliable breast cancer margin assessment tool in the operating room so that further surgery can be continued if necessary to reduce re-excision rate. In this study, we seek to develop a sensitive and specific molecular probe to help surgeons assess if the surgical margin is clean. The molecular probe consists of the unique aqueous quantum dots developed in our laboratory conjugated with antibodies specific to breast cancer markers such as Tn-antigen. Excised tumors from tumor-bearing nude mice were used to demonstrate the method. AQD-Tn mAb probe proved to be sensitive and specific to identify cancer area quantitatively without being affected by the heterogeneity of the tissue. The integrity of the surgical specimen was not affected by the AQD treatment. Furthermore, AQD-Tn mAb method could determine margin status within 30 minutes of tumor excision, indicating its potential as an accurate intraoperative margin assessment method.


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