دورية أكاديمية
Dynamic Contrast-Enhanced Magnetic Resonance Imaging as Imaging Biomarker for Vascular Normalization Effect of Infigratinib in High-FGFR-Expressing Hepatocellular Carcinoma Xenografts.
| العنوان: | Dynamic Contrast-Enhanced Magnetic Resonance Imaging as Imaging Biomarker for Vascular Normalization Effect of Infigratinib in High-FGFR-Expressing Hepatocellular Carcinoma Xenografts. |
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| المؤلفون: | Tran A; Department of Oncologic Imaging, National Cancer Centre, Singapore, Singapore., Koh TS; Department of Oncologic Imaging, National Cancer Centre, Singapore, Singapore., Prawira A; Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, 11 Hospital Drive, Singapore, 169610, Singapore., Ho RZW; Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, 11 Hospital Drive, Singapore, 169610, Singapore., Le TBU; Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, 11 Hospital Drive, Singapore, 169610, Singapore., Vu TC; Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, 11 Hospital Drive, Singapore, 169610, Singapore., Hartano S; Department of Oncologic Imaging, National Cancer Centre, Singapore, Singapore., Teo XQ; Functional Metabolism Group, Agency for Science, Technology and Research, Singapore BioImaging Consortium, Singapore, Singapore., Chen WC; Bruker Singapore Pte Ltd, Singapore, Singapore., Lee P; Functional Metabolism Group, Agency for Science, Technology and Research, Singapore BioImaging Consortium, Singapore, Singapore., Thng CH; Department of Oncologic Imaging, National Cancer Centre, Singapore, Singapore. thng.choon.hua@singhealth.com.sg., Huynh H; Laboratory of Molecular Endocrinology, Division of Molecular and Cellular Research, National Cancer Centre, 11 Hospital Drive, Singapore, 169610, Singapore. cmrhth@nccs.com.sg. |
| المصدر: | Molecular imaging and biology [Mol Imaging Biol] 2021 Feb; Vol. 23 (1), pp. 70-83. Date of Electronic Publication: 2020 Sep 09. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Country of Publication: United States NLM ID: 101125610 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1860-2002 (Electronic) Linking ISSN: 15361632 NLM ISO Abbreviation: Mol Imaging Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2005- : New York, NY : Springer Original Publication: New York, NY : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Magnetic Resonance Imaging*, Biomarkers, Tumor/*metabolism , Carcinoma, Hepatocellular/*drug therapy , Contrast Media/*chemistry , Liver Neoplasms/*drug therapy , Neovascularization, Pathologic/*drug therapy , Phenylurea Compounds/*therapeutic use , Pyrimidines/*therapeutic use , Receptors, Fibroblast Growth Factor/*metabolism, Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis/drug effects ; Carcinoma, Hepatocellular/blood supply ; Cell Proliferation/drug effects ; Humans ; Kinetics ; Liver Neoplasms/blood supply ; Mice, SCID ; Perfusion ; Sorafenib/pharmacology ; Sorafenib/therapeutic use ; Tumor Microenvironment/drug effects ; Xenograft Model Antitumor Assays ; Mice |
| مستخلص: | Purpose: Overexpression of fibroblast growth factor receptor (FGFR) contributes to tumorigenesis, metastasis, and poor prognosis of hepatocellular carcinoma (HCC). Infigratinib-a pan-FGFR inhibitor-potently suppresses the growth of high-FGFR-expressing HCCs in part via alteration of the tumor microenvironment and vessel normalization. In this study, we aim to assess the utility of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as a non-invasive imaging technique to detect microenvironment changes associated with infigratinib and sorafenib treatment in high-FGFR-expressing HCC xenografts. Procedures: Serial DCE-MRIs were performed on 12 nude mice bearing high-FGFR-expressing patient-derived HCC xenografts to quantify tumor microenvironment pre- (day 0) and post-treatment (days 3, 6, 9, and 15) of vehicle, sorafenib, and infigratinib. DCE-MRI data were analyzed using extended generalized kinetic model and two-compartment distributed parameter model. After treatment, immunohistochemistry stains were performed on the harvested tumors to confirm DCE-MRI findings. Results: By treatment day 15, infigratinib induced tumor regression (70 % volume reduction from baseline) while sorafenib induced relative growth arrest (185 % volume increase from baseline versus 694 % volume increase from baseline of control). DCE-MRI analysis revealed different changes in microcirculatory parameters upon exposure to sorafenib versus infigratinib. While sorafenib induced microenvironment changes similar to those of rapidly growing tumors, such as a decrease in blood flow (F), fractional intravascular volume (v Conclusions: Our study demonstrated that DCE-MRI is a reliable non-invasive imaging technique to monitor tumor microcirculatory response to FGFR inhibition and VEGF inhibition in high-FGFR-expressing HCC xenografts. Furthermore, the microcirculatory changes from FGFR inhibition manifested early upon treatment initiation and were reliably detected by DCE-MRI, creating possibilities of combinatorial therapy for synergistic effect. |
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| فهرسة مساهمة: | Keywords: Biomarker; DCE-MRI; FGFR; HCC; Vascular normalization |
| المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Biomarkers, Tumor) 0 (Contrast Media) 0 (Phenylurea Compounds) 0 (Pyrimidines) 0 (Receptors, Fibroblast Growth Factor) 9ZOQ3TZI87 (Sorafenib) A4055ME1VK (infigratinib) |
| تواريخ الأحداث: | Date Created: 20200910 Date Completed: 20210825 Latest Revision: 20240226 |
| رمز التحديث: | 20240226 |
| DOI: | 10.1007/s11307-020-01531-7 |
| PMID: | 32909245 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1860-2002 |
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| DOI: | 10.1007/s11307-020-01531-7 |