Evaluation of the heterogeneous tissue distribution of erlotinib in lung cancer using matrix-assisted laser desorption ionization mass spectrometry imaging
| العنوان: | Evaluation of the heterogeneous tissue distribution of erlotinib in lung cancer using matrix-assisted laser desorption ionization mass spectrometry imaging |
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| المؤلفون: | Akinobu Hamada, Kenji Tamura, Ryosuke Tanino, Yasuhiro Fujiwara, Mayu Ohuchi, Hiroaki Aikawa, Mitsuhiro Hayashi, Yukari Tsubata, Takeshi Isobe |
| المصدر: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-6 (2017) |
| بيانات النشر: | Nature Publishing Group UK, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Pathology, medicine.medical_specialty, Lung Neoplasms, medicine.drug_class, lcsh:Medicine, Mass spectrometry imaging, Tyrosine-kinase inhibitor, Article, 03 medical and health sciences, Erlotinib Hydrochloride, Mice, 0302 clinical medicine, Pharmacokinetics, medicine, Distribution (pharmacology), Animals, Humans, Tissue Distribution, Epidermal growth factor receptor, Lung cancer, lcsh:Science, neoplasms, Lung, Protein Kinase Inhibitors, Multidisciplinary, biology, Chemistry, lcsh:R, medicine.disease, Xenograft Model Antitumor Assays, respiratory tract diseases, Matrix-assisted laser desorption/ionization, 030104 developmental biology, 030220 oncology & carcinogenesis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, biology.protein, lcsh:Q, Erlotinib, medicine.drug |
| الوصف: | Although drug distribution in tumor tissues has a significant impact on efficacy, conventional pharmacokinetic analysis has some limitations with regard to its ability to provide a comprehensive assessment of drug tissue distribution. Erlotinib is a tyrosine kinase inhibitor that acts on the epidermal growth factor receptor; however, it is unclear how this drug is histologically distributed in lung cancer. We used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze erlotinib distribution in the tumor and normal lung tissues of a mouse xenograft model and patient with non-small cell lung cancer. LC-MS/MS showed that the erlotinib tissue concentration in the xenograft tumor tissue was clearly lower than that in the normal tissue at the time of maximum blood concentration. MALDI-MSI showed the heterogeneous distribution of erlotinib at various levels in the murine tissues; interestingly, erlotinib was predominantly localized in the area of viable tumor compared to the necrotic area. In the patient-derived tissue, MALDI-MSI showed that there were different concentrations of erlotinib distributed within the same tissue. For drug development and translational research, the imaging pharmacokinetic study used the combination of MALDI-MSI and LC-MS/MS analyses may be useful in tissues with heterogeneous drug distribution. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e33264308215783a56bc2fe45a10defTest http://europepmc.org/articles/PMC5626687Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1e33264308215783a56bc2fe45a10def |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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