Monitoring Tumor Response to Linifanib Therapy with SPECT/CT Using the Integrin αvβ3–Targeted Radiotracer 99mTc-3P-RGD2
العنوان: | Monitoring Tumor Response to Linifanib Therapy with SPECT/CT Using the Integrin αvβ3–Targeted Radiotracer 99mTc-3P-RGD2 |
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المؤلفون: | Yanping Luo, Guoqiang Shao, Martin J. Voorbach, Yumin Zhang, Yang Zhou, Shuang Liu, Daniel H. Albert, Sarah R. Mudd, Shundong Ji, Gerard B. Fox |
بيانات النشر: | The American Society for Pharmacology and Experimental Therapeutics, 2013. |
سنة النشر: | 2013 |
مصطلحات موضوعية: | Male, Indazoles, chemistry.chemical_element, Mice, Nude, Angiogenesis Inhibitors, Single-photon emission computed tomography, Technetium, Multimodal Imaging, Peptides, Cyclic, chemistry.chemical_compound, Drug Discovery and Translational Medicine, Mice, Prostate, Glioma, Percent Injected Dose, medicine, Biomarkers, Tumor, Animals, Humans, Pharmacology, medicine.diagnostic_test, business.industry, Phenylurea Compounds, Prostatic Neoplasms, Organotechnetium Compounds, Protein-Tyrosine Kinases, medicine.disease, Integrin alphaVbeta3, Xenograft Model Antitumor Assays, Linifanib, medicine.anatomical_structure, chemistry, Positron emission tomography, Positron-Emission Tomography, Molecular Medicine, Immunohistochemistry, Female, Radiopharmaceuticals, business, Nuclear medicine, Tomography, X-Ray Computed, Dimerization, Oligopeptides |
الوصف: | The objective of this study was to determine the utility of (99m)Tc-3P-Arg-Gly-Asp (RGD2) single photon emission computed tomography (SPECT)/computed tomography (CT) for noninvasive monitoring of integrin αvβ3-expression response to antiangiogenic treatment with linifanib. Linifanib or vehicle therapy was carried out in female athymic nu/nu mice bearing U87MG glioma (high αvβ3 expression) or PC-3 prostate (low αvβ3 expression) tumors at 12.5 mg/kg twice daily. The average tumor volume was 180 ± 90 mm(3) the day prior to baseline SPECT/CT. Longitudinal (99m)Tc-3P-RGD2 SPECT/CT imaging was performed at baseline (-1 day) and days 1, 4, 11, and 18. Tumors were harvested at all imaging time points for histopathological analysis with HE and immunohistochemistry. A significant difference in tumor volumes between vehicle- and linifanib-treated groups was observed after 4 days of linifanib therapy in the U87MG model. The percent injected dose (%ID) tumor uptake of (99m)Tc-3P-RGD2 peaked in the vehicle-treated group at day 11, while the %ID/cm(3) tumor uptake decreased slowly over the whole study period. During the first 2 days of linifanib treatment, a rapid decrease in both %ID/cm(3) tumor uptake and tumor/muscle ratios of (99m)Tc-3P-RGD2 was observed, followed by a slow decrease until day 18. No decrease in tumor uptake of (99m)Tc-3P-RGD2 or tumor volume was observed for either treatment group in the PC-3 model. Changes in tumor vasculature were confirmed by histopathological HE analysis and immunohistochemistry. Longitudinal imaging using (99m)Tc-3P-RGD2 SPECT/CT may be a useful tool for monitoring the downstream biologic effects of linifanib therapy. |
اللغة: | English |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::af75c3aa70f6531224133aac210515b6 https://europepmc.org/articles/PMC3716312/ |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....af75c3aa70f6531224133aac210515b6 |
قاعدة البيانات: | OpenAIRE |
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