Inhibition of MDA-MB-231 cell proliferation by pHLIP(Var7)-P1AP and SPECT imaging of MDA-MB-231 breast cancer-bearing nude mice using 125I-pHLIP(Var7)-P1AP

2021 ◽  
Author(s):  
Yue Hua Chen ◽  
Ming Ming Yu ◽  
Zhen Guang Wang

Abstract Aim To observe the effect of pHLIP(Var7)-P1AP on the proliferation of MDA-MB-231 triple-negative breast cancer cells and the small-animal single-photon-emission computed tomography (SPECT) imaging of breast cancer–bearing mice carrying MDA-MB-231 cells. Methods Peptide pHLIP(Var7)-P1AP was synthesized by solid-phase peptide synthesis. The binding of fluorescently labeled pHLIP(Var7)-P1AP to MDA-MB-231 cells under various pH conditions and its effect on MDA-MB-231 cell proliferation were analyzed. pHLIP(Var7)-P1AP was labeled with 125I, and the biological distribution of 125I-pHLIP(Var7)-P1AP in the breast cancer mouse model carrying MDA-MB-231 cells as well as the outcome of small-animal SPECT imaging were evaluated. Results pHLIP(Var7)-P1AP was successfully synthesized. Under pH 6.0, fluorescently labeled pHLIP(Var7)-P1AP had a higher binding ability to MDA-MB-231 cells and significantly inhibited the proliferation of MDA-MB-231 cells. The labeling efficiency of pHLIP(Var7)-P1AP with 125I was 33.1 ± 2.7 %, and the radiochemical purity was 98.5 ± 1.8 %. 125I-pHLIP(Var7)-P1AP showed a high concentration in tumors. Small-animal SPECT imaging showed clearly visible tumors at 4 h after injection. Conclusions In the acidic environment, pHLIP(Var7)-P1AP can efficiently target MDA-MB-231 cells and inhibit their growth. Small-animal SPECT of 125I-pHLIP(Var7)-P1AP can clearly image tumors.

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.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 358 ◽  
Author(s):  
Ayman Abouzayed ◽  
Cheng-Bin Yim ◽  
Bogdan Mitran ◽  
Sara S. Rinne ◽  
Vladimir Tolmachev ◽  
...  

Gastrin-releasing peptide receptor (GRPR) and prostate-specific membrane antigen (PSMA) are overexpressed in most prostate cancers. GRPR expression is higher in early stages while PSMA expression increases with progression. The possibility of targeting both markers with a single theranostics radiotracer could improve patient management. Three GRPR/PSMA-targeting bispecific heterodimers (urea derivative PSMA-617 and bombesin-based antagonist RM26 linked via X-triazolyl-Tyr-PEG2, X = PEG2 (BO530), (CH2)8 (BO535), none (BO536)) were synthesized by solid-phase peptide synthesis. Peptides were radio-iodinated and evaluated in vitro for binding specificity, cellular retention, and affinity. In vivo specificity for all heterodimers was studied in PC-3 (GRPR-positive) and LNCaP (PSMA-positive) xenografts. [125I]I-BO530 was evaluated in PC-3pip (GRPR/PSMA-positive) xenografts. Micro single-photon emission computed tomography/computed tomography (microSPECT/CT) scans were acquired. The heterodimers were radiolabeled with high radiochemical yields, bound specifically to both targets, and demonstrated high degree of activity retention in PC-3pip cells. Only [125I]I-BO530 demonstrated in vivo specificity to both targets. A biodistribution study of [125I]I-BO530 in PC-3pip xenografted mice showed high tumor activity uptake (30%–35%ID/g at 3 h post injection (pi)). Activity uptake in tumors was stable and exceeded all other organs 24 h pi. Activity uptake decreased only two-fold 72 h pi. The GRPR/PSMA-targeting heterodimer [125I]I-BO530 is a promising agent for theranostics application in prostate cancer.


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.


2001 ◽  
Vol 35 (3) ◽  
pp. 359-363 ◽  
Author(s):  
Javier Garcia-Campayo ◽  
Concepcion Sanz-Carrillo ◽  
Teresa Baringo ◽  
Concepción Ceballos

Objective: There are no previous studies using single photon emission computed tomography (SPECT) scans in somatization disorder (SD) patients. The aim of this paper is to assess SPECT imaging abnormalities in SD patients and study any relation to laterality. Method: Eleven SD patients from the Somatization Disorder Unit of Miguel Servet University Hospital, Zaragoza, Spain, not fulfilling criteria for any other psychiatric disorder and showing normal computed tomography (CT) and magnetic resonance imaging (MRI) images were studied with SPECT. Patients with DSM-IV axis I comorbidity were ruled out because it has been demonstrated that SPECT scans can show abnormalities in patients with depression and anxiety disorders. The technique used for SPECT was 99mTc-D,1,hexamethylpropyleneamide- oxime (99mTc-HMPAO) in four patients and 99mTc-bicisate in the other seven. The SPECT scans were evaluated without knowledge of clinical data and entirely by visual inspection. Results: Seven out of 11 (63.6%) SD patients showed hypoperfusion in SPECT imaging. In four cases there was hypoperfusion in the non-dominant hemisphere and the predominance of pain symptoms took place in the contralateral hemibody. In the other three patients hypoperfusion was bilateral. The anatomical regions affected were cerebellum (four cases), frontal and prefrontal areas (three cases), temporoparietal areas (two cases) and the complete hemisphere (one case). Conclusions: A proportion of SD patients may present hypoperfusion in SPECT images, uni- or bilaterally, in different brain areas. Possible aetiological explanations for this finding are discussed. Controlled studies are necessary to confirm or refute this hypothesis.


Nanomaterials ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 660 ◽  
Author(s):  
Ha Shim ◽  
Jung Yang ◽  
Sun-Wook Jeong ◽  
Chang Lee ◽  
Lee Song ◽  
...  

Increasing concerns regarding the adverse effects of radioactive iodine waste have inspired the development of a highly efficient and sustainable desalination process for the treatment of radioactive iodine-contaminated water. Because of the high affinity of silver towards iodine species, silver nanoparticles immobilized on a cellulose acetate membrane (Ag-CAM) and biogenic silver nanoparticles containing the radiation-resistant bacterium Deinococcus radiodurans (Ag-DR) were developed and investigated for desalination performance in removing radioactive iodines from water. A simple filtration of radioactive iodine using Ag-CAM under continuous in-flow conditions (approximately 1.5 mL/s) provided an excellent removal efficiency (>99%) as well as iodide anion-selectivity. In the bioremediation study, the radioactive iodine was rapidly captured by Ag-DR in the presence of high concentration of competing anions in a short time. The results from both procedures can be visualized by using single-photon emission computed tomography (SPECT) scanning. This work presents a promising desalination method for the removal of radioactive iodine and a practical application model for remediating radioelement-contaminated waters.


2022 ◽  
Vol 15 (1) ◽  
pp. 96
Author(s):  
Elisabeth Plhak ◽  
Edith Gößnitzer ◽  
Reingard M. Aigner ◽  
Herbert Kvaternik

Dopaminergic transporter (DAT) imaging with single photon emission computed tomography (SPECT) is used to diagnose Parkinson’s disease and to differentiate it from other neurodegenerative disorders without presynaptic dopaminergic dysfunction. The radioiodinated tropane alkaloids [123I]FP-CIT and [123I]β-CIT enable the evaluation of the integrity of DATs. Commonly, the labeling of these compounds is performed by electrophilic substitution of the alkylstannylated precursors with radioactive iodine and following purification by HPLC or solid phase extraction (SPE). This work presents the first radioiodination of β-CIT and FP-CIT with no carrier added [131I]NaI on a Scintomics GRP synthesis module. Free iodine-131 and impurities were removed by SPE over a C-18 Sep-Pak cartridge. We achieved a radiochemical yield of >75% and a radiochemical purity of >98% with both compounds. Our development of an automated synthesis on a commercially available synthesizer ensures robust and efficient labeling of [131I]FP-CIT and [131I]β-CIT starting with low concentrated radioiodine.


Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5459
Author(s):  
Huiling Li ◽  
Zhen Liu ◽  
Lujie Yuan ◽  
Kevin Fan ◽  
Yongxue Zhang ◽  
...  

Breast cancer is a malignant tumor that can affect women worldwide and endanger their health and wellbeing. Early detection of breast cancer can significantly improve the prognosis and survival rate of patients, but with traditional anatomical imagine methods, it is difficult to detect lesions before morphological changes occur. Radionuclide-based molecular imaging based on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) displays its advantages for detecting breast cancer from a functional perspective. Radionuclide labeling of small metabolic compounds can be used for imaging biological processes, while radionuclide labeling of ligands/antibodies can be used for imaging receptors. Noninvasive visualization of biological processes helps elucidate the metabolic state of breast cancer, while receptor-targeted radionuclide molecular imaging is sensitive and specific for visualization of the overexpressed molecular markers in breast cancer, contributing to early diagnosis and better management of cancer patients. The rapid development of radionuclide probes aids the diagnosis of breast cancer in various aspects. These probes target metabolism, amino acid transporters, cell proliferation, hypoxia, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), gastrin-releasing peptide receptor (GRPR) and so on. This article provides an overview of the development of radionuclide molecular imaging techniques present in preclinical or clinical studies, which are used as tools for early breast cancer diagnosis.


Author(s):  
Abass Alavi ◽  
Andrew B. Newberg

Functional neuroimaging with positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI) can be highly useful in the evaluation and management of patients with psychiatric disorders. PET and SPECT imaging typically evaluate cerebral metabolism and blood flow, respectively, and can determine patterns associated with different disorders such as depression or schizophrenia. PET and SPECT imaging can also evaluate neurotransmitter changes such as dopamine or serotonin associated with different psychiatric disorders. fMRI is an excellent tool for studying the effects of psychiatric disorders on specific brain processes related to cognition and mood. fMRI activations studies allow researchers to present various stimuli to a subject in order to determine how the brain reacts and whether psychiatric disorders are associated with different brain reactivity patterns. Functional neuroimaging with PET, SPECT, and fMRI can be highly useful in the investigation of the mechanism of action of integrative therapies for psychiatric disorders.


Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581988254
Author(s):  
Wei Sun ◽  
Guifu He ◽  
Mingming Zhang ◽  
Yi Zhao ◽  
Hongmei Yu ◽  
...  

Aims: Our study was designed to investigate the usefulness of 99mTc-3PRGD2 single-photon emission computed tomography (SPECT) for noninvasively monitoring the response of integrin αvβ3 expression to antiangiogenic treatment with endostar and cisplatin in xenograft animals. Methods: 99mTc-3PRGD2 SPECT imaging was performed at days 0, 7, 14, and 21. Tumors were harvested at all imaging time points for Western blotting and histopathological analysis. Result: In 99mTc-3PRGD2 SPECT imaging, the radioactivity accumulation of NaCl group rised gradually in the first half and dispersed on day 21 due to the necrosis of the tumor. While the radioactivity accumulation of treated groups gradually decreased throughout the course. The downtrend of tumor to nontumor ratio in endostar-treated group was more remarkable than cisplatin-treated group. The expression of intergrin αvβ3 of treated groups was lower than NaCl group from day 14. The expression of intergrin αvβ3 of endostar-treated group was significantly lower than cisplatin-treated group from baseline onward. Conclusion: It’s demonstrated that the 99mTc-3PRGD2 could noninvasively visualize and semiquantify tumor angiogenesis in the xenograft model and monitor the response to the antiangiogenic therapy of endostar and cisplatin effectively. It also can predict the outcome of endostar and cisplatin therapy in xenograft animals.


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