Some thyroid-disrupting chemicals (TDCs) affect thyroid function by activating the pathways mediated by a typical thyroid hormone (TH) membrane receptor, integrin α_vβ₃. The present study introduces improved competitive binding assays for the rapid and sensitive evaluation of the binding affinities of TDCs for integrin α_vβ_3. Based on different probes, two assays were modified: a fluorescence competitive binding assay and a radioligand competitive binding assay. The chemicals tested included the known TH, 3,3',5,5'-tetraiodo-l-thyronine (T4); a deaminated analog of T4, tetraiodothyroacetic acid (tetrac); and phthalate esters (PAEs). The relative binding potency of T4 was studied, and the concentration required to displace 50% of the ligands from their receptors (RIC50) of T4 was 4.9 × 10⁵ and 9.7 × 10⁴ nM for the fluorescence and radioligand competitive binding assays, respectively, suggesting that the radioligand competitive binding assay might be more sensitive for the evaluation of the binding affinity for integrin α_vβ₃. The three PAEs, including diethyl hexyl phthalate (DEHP), benzyl butyl phthalate (BBP) and dibutyl phthalate (DnBP), demonstrated binding affinities for integrin α_vβ₃ in the following order of potency: DnBP > DEHP > BBP tested by the radioligand competitive binding assay. A docking simulation of each of the three PAEs with integrin α_vβ₃ confirmed the calculated binding energies, which had a strong positive relationship with the log RIC20 values of the 3 PAEs (R = 0.99, p < 0.001). The present study shows that the established radioligand competitive binding assay could be used as a valuable tool for quantifying the affinity of TDCs for integrin α_vβ₃.

01 Oct 2018·Molecular Imaging and BiologyQ3 · MEDICINE

Comparison of [99mTc]3PRGD2 Imaging and [18F]FDG PET/CT in Breast Cancer and Expression of Integrin αvβ3 in Breast Cancer Vascular Endothelial Cells

Q3 · MEDICINE

Article

Author: Chen, Xiangjin ; Miao, Weibing ; Huang, Chao ; Li, Fang ; Chen, Zhenying ; Fu, Fangmeng ; Zhu, Zhaohui ; Yang, Yinghong ; Zheng, Shan ; Jia, Bing

PURPOSEThis study aimed to investigate the value of ^99mtechnetium-three polyethylene glycol spacers-arginine-glycine-aspartic acid ([^99mTc]3PRGD₂) imaging in diagnosis and staging of breast cancer compared with 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) imaging, and to explore the expression of integrin α_vβ₃ in tumor vascular endothelial cells.PROCEDURESForty-two women with suspected breast cancer underwent both [^99mTc]3PRGD₂ imaging and [¹⁸F]FDG imaging. Visual analysis was used to assess primary breast lesion, axillary lymph node, and distant metastasis. The tumor-blood (T/B) ratios from [^99mTc]3PRGD₂ imaging and the maximum standardized uptake value (SUVmax) from [¹⁸F]FDG imaging were analyzed for breast lesions. Integrin α_vβ₃ was analyzed through immunohistochemistry.RESULTSForty-five breast lesions were found (malignant, n = 38; benign, n = 7). The sensitivity, specificity, and accuracy of [^99mTc]3PRGD₂ and [¹⁸F]FDG imaging in visual analysis for the breast lesion were 97.4, 87.5, and 95.6 % and 97.4, 71.4, and 93.3 %, respectively (P > 0.05). For semi-quantitative analysis, no significant difference of the area under the curves (AUC) was found in the imaging using the two radiopharmaceuticals (0.880 and 0.955; Z = 0.88, P > 0.05). The sensitivity, specificity, and accuracy for axillary lymph node metastasis with [^99mTc]3PRGD₂ and [¹⁸F]FDG were 78.05, 99.36, and 94.92 % and 85.37, 98.72, and 95.64 %, respectively (P > 0.05). Nine patients with distant metastases were all detected with the two radiopharmaceuticals. The expression of integrin α_vβ₃ was correlated with [^99mTc]3PRGD₂ uptake (r = 0.582, P = 0.001), which were significantly higher in the HER2-positive and stage III-IV patients (P < 0.05).CONCLUSIONSThe prospective study demonstrated that [^99mTc]3PRGD₂ imaging seems to be valuable for diagnosis of breast cancer and its staging. It may be less sensitive for detecting small lymph node metastatic lesions when compared with [¹⁸F]FDG imaging. Integrin α_vβ₃ in tumor microvessels was associated with the breast cancer subtype and its staging.

01 Sep 2018·Journal of Chromatography BQ3 · MEDICINE

An optimized LC-MS/MS method for determination of HYNIC-3PRGD2, a new promising imaging agent for tumor targeting, in rat plasma and its application

Q3 · MEDICINE

Article

Author: Niu, Liyun ; Wang, Xinyu ; Zhu, Xiaoxia ; Wu, Zhuona ; Jia, Bing ; Dou, Guifang ; Meng, Zhiyun ; Li, Jian ; Gu, Ruolan ; Gan, Hui ; Wang, Fan ; Ma, Baiping

HYNIC-3PRGD₂ is used to prepare a new ^99mTc-radiolabeled tracer. HYNIC-3PRGD₂, which has a high binding affinity for the integrin α_vβ₃ due to its special structure, has become a promising tumor imaging agent for diagnosis and monitor of the clinical response to therapeutic effects of anti-tumor agents. Here, we developed and validated a method for determination of HYNIC-3PRGD₂ concentration in rat plasma using ultra-high performance liquid chromatography-tandem mass spectrometry system. Following sample extraction by methanol precipitation, satisfactory separation through chromatography was achieved on an hydrophilic reverse-phase C₁₈ column AQ (2.1 mm × 100 mm, 2.7 μm) at a flow rate of 0.2 mL·min^-1 with an gradient elution using mobile phase consisting of ultrapure water and acetonitrile fortified with 0.1% formic acid respectively. The calibration curve was developed over a linear range of 3.125-100 ng·mL^-1 with the lower limit of quantification of 3.125 ng·mL^-1. The HYNIC-3PRGD₂ and its internal standard c(RGDfK)(RK5) were detected and quantified with the multiple reaction monitoring (MRM) mode on a triple-quadrupole tandem mass spectrometer. This method was successfully validated and applied for pharmacokinetic evaluation of HYNIC-3PRGD₂ during pre-clinical experiments.

100 Deals associated with 99mTc-3P4-RGD2

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Pubmed \| Eur J Nucl Med Mol Imaging	Not Applicable	Solitary Pulmonary Nodule integrin α(ν)β(3)	21	99mTc-3P4-RGD2	efywmyqlpk(gsyozcebru) = qcwumfpwys peamsncfok (fubyohivie ) View more	-	01 Dec 2011

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