scholarly journals An Experimental Study on [125I]I-pHLIP (Var7) for SPECT/CT Imaging of an MDA-MB-231 Triple-Negative Breast Cancer Mouse Model by Targeting the Tumor Microenvironment

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mingming Yu ◽  
Yanqin Sun ◽  
Guangjie Yang ◽  
Zhenguang Wang

Objective. To evaluate the diagnostic efficacy of MDA-MB-231 triple-negative breast cancer with 125I-labeled pHLIP (Var7) by single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. Methods. The binding fraction of [125I]I-pHLIP (Var7) and MDA-MB-231 cells was measured at pH 7.4 and pH 6.0, and tumor-bearing mice were subjected to small-animal SPECT/CT imaging studies. Results. At pH = 6.0 , the binding fractions of [125I]I-pHLIP (Var7) and MDA-MB-231 cells at 10 min, 40 min, 1 h, and 2 h were 1 .9 ± 0.1 %, 3.5 ± 0.1 %, 6.3 ± 0.8 %, and 6.6 ± 0.3 %, respectively. At pH = 7.4 , there was no measured binding between [125I]I-pHLIP (Var7) and MDA-MB-231 cells. Small-animal SPECT/CT imaging showed clearly visible tumors at 1 and 2 h after injection. Conclusions. [125I]I-pHLIP (Var7) could bind to MDA-MB-231 cells in an acidic environment, and small-animal SPECT/CT imaging showed clear tumors at 1 and 2 h after probe injection.

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1039
Author(s):  
Montemagno ◽  
Dumas ◽  
Cavaillès ◽  
Ahmadi ◽  
Bacot ◽  
...  

Recent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). Our objective was to perform the in vivo imaging of VCAM-1 in mice models of TNBC. The Cancer Genomic Atlas (TCGA) database was analyzed to evaluate the prognostic role of VCAM-1 in TNBC. MDA-MB-231 (VCAM-1+) and control HCC70 (VCAM-1-) TNBC cells were subcutaneously xenografted in mice and VCAM-1 expression was assessed in vivo by single-photon emission computed tomography (SPECT) imaging using 99mTc-cAbVCAM1-5. Then, MDA-MB-231 cells were intravenously injected in mice and VCAM-1 expression in lung metastasis was assessed by SPECT imaging after 8 weeks. TCGA analysis showed that VCAM-1 is associated with a poor prognosis in TNBC patients. In subcutaneous tumor models, 99mTc-cAbVCAM1-5 uptake was 2-fold higher in MDA-MB-231 than in HCC70 (p < 0.01), and 4-fold higher than that of the irrelevant control (p < 0.01). Moreover, 99mTc-cAbVCAM1-5 uptake in MDA-MB-231 lung metastases was also higher than that of 99mTc-Ctl (p < 0.05). 99mTc-cAbVCAM1-5 is therefore a suitable tool to evaluate the role of VCAM-1 as a marker of tumor aggressiveness of TNBC.


Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4719
Author(s):  
Anzhelika Vorobyeva ◽  
Ekaterina Bezverkhniaia ◽  
Elena Konovalova ◽  
Alexey Schulga ◽  
Javad Garousi ◽  
...  

Efficient treatment of disseminated triple-negative breast cancer (TNBC) remains an unmet clinical need. The epithelial cell adhesion molecule (EpCAM) is often overexpressed on the surface of TNBC cells, which makes EpCAM a potential therapeutic target. Radionuclide molecular imaging of EpCAM expression might permit selection of patients for EpCAM-targeting therapies. In this study, we evaluated a scaffold protein, designed ankyrin repeat protein (DARPin) Ec1, for imaging of EpCAM in TNBC. DARPin Ec1 was labeled with a non-residualizing [125I]I-para-iodobenzoate (PIB) label and a residualizing [99mTc]Tc(CO)3 label. Both imaging probes retained high binding specificity and affinity to EpCAM-expressing MDA-MB-468 TNBC cells after labeling. Internalization studies showed that Ec1 was retained on the surface of MDA-MB-468 cells to a high degree up to 24 h. Biodistribution in Balb/c nu/nu mice bearing MDA-MB-468 xenografts demonstrated specific uptake of both [125I]I-PIB-Ec1 and [99mTc]Tc(CO)3-Ec1 in TNBC tumors. [125I]I-PIB-Ec1 had appreciably lower uptake in normal organs compared with [99mTc]Tc(CO)3-Ec1, which resulted in significantly (p < 0.05) higher tumor-to-organ ratios. The biodistribution data were confirmed by micro-Single-Photon Emission Computed Tomography/Computed Tomography (microSPECT/CT) imaging. In conclusion, an indirectly radioiodinated Ec1 is the preferable probe for imaging of EpCAM in TNBC.


Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1796
Author(s):  
Rafi Kabarriti ◽  
N. Patrik Brodin ◽  
Hillary Yaffe ◽  
Mark Barahman ◽  
Wade R. Koba ◽  
...  

Radiation therapy (RT) has traditionally not been widely used in the management of hepatic malignancies for fear of toxicity in the form of radiation-induced liver disease (RILD). Pre-clinical hepatic irradiation models can provide clinicians with better understanding of the radiation tolerance of the liver, which in turn may lead to the development of more effective cancer treatments. Previous models of hepatic irradiation are limited by either invasive laparotomy procedures, or the need to irradiate the whole or large parts of the liver using external skin markers. In the setting of modern-day radiation oncology, a truly translational animal model would require the ability to deliver RT to specific parts of the liver, through non-invasive image guidance methods. To this end, we developed a targeted hepatic irradiation model on the Small Animal Radiation Research Platform (SARRP) using contrast-enhanced cone-beam computed tomography image guidance. Using this model, we showed evidence of the early development of region-specific RILD through functional single photon emission computed tomography (SPECT) imaging.


2020 ◽  
Vol 14 (5) ◽  
pp. 629-638
Author(s):  
Mohd Fazrin Mohd Rohani ◽  
Siti Nurshahirah Mohd Yonan ◽  
Nashrulhaq Tagiling ◽  
Wan Mohd Nazlee Wan Zainon ◽  
Yusri Udin ◽  
...  

Study DesignRetrospective study.PurposeThis study aims to semiquantitatively evaluate the standardized uptake value (SUV) of 99mTc-methylene diphosphonate (MDP) radionuclide tracer in the normal vertebrae of breast cancer patients using an integrated single-photon emission computed tomography (SPECT)/computed tomography (CT) scanner.Overview of LiteratureMolecular imaging techniques using gamma cameras and stand-alone SPECT have traditionally been utilized to evaluate metastatic bone diseases. However, these methods lack quantitative analysis capabilities, impeding accurate uptake characterization.MethodsA total of 30 randomly selected female breast cancer patients were enrolled in this study. The SUV mean (SUVmean) and SUV maximum (SUVmax) values for 286 normal vertebrae at the thoracic and lumbar levels were calculated based on the patients’ body weight (BW), body surface area (BSA), and lean body mass (LBM). Additionally, 106 degenerative joint disease (DJD) lesions of the spine were also characterized, and both their BW SUVmean and SUVmax values were obtained. A receiver operating characteristic (ROC) curve analysis was then performed to determine the cutoff value of SUV for differentiating DJD from normal vertebrae.ResultsThe mean±standard deviations for the SUVmean and SUVmax in the normal vertebrae displayed a relatively wide variability: 3.92±0.27 and 6.51±0.72 for BW, 1.05±0.07 and 1.75±0.17 for BSA, and 2.70±0.19 and 4.50±0.44 for LBM, respectively. Generally, the SUVmean had a lower coefficient of variation than the SUVmax. For DJD, the mean±standard deviation for the BW SUVmean and SUVmax was 5.26±3.24 and 7.50±4.34, respectively. Based on the ROC curve, no optimal cutoff value was found to differentiate DJD from normal vertebrae.ConclusionsIn this study, the SUV of 99mTc-MDP was successfully determined using SPECT/CT. This research provides an approach that could potentially aid in the clinical quantification of radionuclide uptake in normal vertebrae for the management of breast cancer patients.


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