https://scholars.lib.ntu.edu.tw/handle/123456789/414806
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | C. W. Huang | en US |
dc.contributor.author | W. C. Hsieh | en US |
dc.contributor.author | S. T. Hsu | en US |
dc.contributor.author | Y. W. Lin | en US |
dc.contributor.author | Y. H. Chung | en US |
dc.contributor.author | W. C. Chang | en US |
dc.contributor.author | H. Chiu | en US |
dc.contributor.author | Y. H. Lin | en US |
dc.contributor.author | C. P. Wu | en US |
dc.contributor.author | T. C. Yen | en US |
dc.contributor.author | F. T. Huang | en US |
dc.creator | F. T. Huang;T. C. Yen;C. P. Wu;Y. H. Lin;H. Chiu;W. C. Chang;Y. H. Chung;Y. W. Lin;S. T. Hsu;W. C. Hsieh;C. W. Huang | - |
dc.date.accessioned | 2019-07-24T01:41:09Z | - |
dc.date.available | 2019-07-24T01:41:09Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 18387640 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/414806 | - |
dc.description.abstract | PURPOSE: Growing evidence has demonstrated that aberrant expression of integrin α2β1 might contribute to the invasion, metastasis and drug resistance of non-small cell lung cancer (NSCLC). Thus, the integrin α2β1 targeting 68Ga-DOTA-A2B1 tracer was validated in NSCLC in contrast to accumulation of the clinically used 18F-FDG PET tracer to see if 68Ga-DOTA-A2B1-PET imaging can offer a valuable and critical diagnostic imaging criterion for the identification of phenotypes of aggressive lung cancer. METHODS: To verify the prognostic value of integrin α2β1, several quantitative and functional in vitro assays were validated in different NSCLC cell lines (CL1-0, CL1-5, A549 and selected A549++ cells). Positron emission tomography (PET) imaging studies using both standard 18F-FDG and a newly developed 68Ga-labeled integrin α2β1 (68Ga-DOTA-A2B1) tracer were sequentially performed on mice with lung tumor xenografts in different anatomic locations (subcutaneous, orthotopic and osseous) to validate the targeting capability of the 68Ga-DOTA-A2B1 tracers. Treatment responses were monitored by injecting animals with metastatic bone tumors with 5 mg/kg doxorubicin. All in vivo treatment responses in each treatment subgroup were monitored with a PET imaging system to evaluate the up-regulation of integrin expression at the earliest stage of treatment (6 h). RESULTS: The PET and computed tomography (CT) images from NSCLC xenograft animals unambiguously demonstrated accumulation of the integrin tracer 68Ga-DOTA-A2B1 in the tumor lesions at all locations. The average tumor uptake and tumor-to-normal (T/N) ratio were 2.51 ± 0.56 %ID/g and T/N = 2.82, 3.40 ± 0.42 %ID/g and T/N = 1.52, and 1.58 ± 0.108 %ID/g and T/N = 2.31 in subcutaneous, orthotopic and osseous tumors, respectively (n = 5; p < 0.05). The xenograft tumors were all clearly visible. In contrast, the accumulation of 18F-FDG reached 3.6 ± 0.76 %ID/g, 1.39 ± 0.075 %ID/g and 3.78 ± 0.73 %ID/g in subcutaneous, orthotopic and osseous tumors, respectively (n = 5; p < 0.05). However, due to the high background uptake by normal tissue, the T/N values were less than or close to 1, making the tumors almost indistinguishable in the PET imaging analysis. Furthermore, 68Ga-DOTA-A2B1-PET imaging of the treated osseous tumor model demonstrated more than 19% tracer uptake in A549 lesions (1.72 ± 0.95 %ID/g vs. pretreatment 1.44 ± 0.12 %ID/g,p = 0. 015) 6 h post-treatment with doxorubicin. The elevated intensity of tracer uptake was in accordance with the results of in vitroWestern blot and ex vivo integrin staining, demonstrating elevated integrin α2β1 expression. CONCLUSION: In this study, integrin α2β1 was identified as a biomarker of aggressive malignant NSCLC. Thus, efforts should be devoted to validating integrin α2β1 as a potential target for non-invasive diagnosis and as a predictive marker for monitoring treatment responses using a preclinical PET imaging system. ? Ivyspring International Publisher. | - |
dc.publisher | Ivyspring International Publisher | - |
dc.relation.ispartof | Theranostics | - |
dc.subject | Integrin α2β1; Non-small cell lung cancer; Phenotyping imaging; Positron emission tomography; Treatment response monitoring | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | doxorubicin; fluorodeoxyglucose f 18; gallium 68; very late activation antigen 2; very late activation antigen 2; animal experiment; animal model; Article; cancer diagnosis; cancer prognosis; controlled study; human; human cell; image analysis; in vitro study; in vivo study; lung cancer cell line; male; mouse; non small cell lung cancer; nonhuman; phenotype; positron emission tomography; protein expression; single drug dose; treatment response; tumor localization; upregulation; A-549 cell line; animal; diagnostic imaging; drug resistance; genetics; immunohistochemistry; lung tumor; metabolism; non small cell lung cancer; positron emission tomography; procedures; tumor cell line; A549 Cells; Animals; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Drug Resistance, Neoplasm; Humans; Immunohistochemistry; Integrin alpha2beta1; Lung Neoplasms; Mice; Positron-Emission Tomography | - |
dc.title | The use of PET imaging for prognostic integrin α2β1 phenotyping to detect non-small cell lung cancer and monitor drug resistance responses | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.7150/thno.19304 | - |
dc.relation.pages | 4013-4028 | - |
dc.relation.journalvolume | 7 | - |
dc.relation.journalissue | 16 | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
crisitem.author.dept | Biochemical Science and Technology | - |
crisitem.author.orcid | 0000-0002-3671-8992 | - |
crisitem.author.parentorg | College of Life Science | - |
顯示於: | 生化科技學系 |
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