Evaluation of Two Optical Probes for Imaging the Integrin αvβ6− In Vitro and In Vivo in Tumor-Bearing Mice
| العنوان: | Evaluation of Two Optical Probes for Imaging the Integrin αvβ6− In Vitro and In Vivo in Tumor-Bearing Mice |
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| المؤلفون: | Julie L. Sutcliffe, Nadine Bauer, Tanushree Ganguly, Sarah Y. Tang |
| المصدر: | Molecular Imaging and Biology. 22:1170-1181 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cancer Research, Biodistribution, Fluorescence-lifetime imaging microscopy, Chemistry, media_common.quotation_subject, medicine.disease, 030218 nuclear medicine & medical imaging, law.invention, 03 medical and health sciences, 0302 clinical medicine, Oncology, In vivo, Pancreatic tumor, Confocal microscopy, law, Cancer research, medicine, Radiology, Nuclear Medicine and imaging, Internalization, Preclinical imaging, Ex vivo, media_common |
| الوصف: | The purpose of this study was to develop and evaluate two αvβ6-targeted fluorescent imaging agents. The integrin subtype αvβ6 is significantly upregulated in a wide range of epithelial derived cancers, plays a key role in invasion and metastasis, and expression is often located at the invasive edge of tumors. αvβ6-targeted fluorescent imaging agents have the potential to guide surgical resection leading to improved patient outcomes. Both imaging agents were based on the bi-PEGylated peptide NH2-PEG28-A20FMDV2-K16R-PEG28 (1), a peptide that has high affinity and selectivity for the integrin αvβ6: (a) 5-FAM-X-PEG28-A20FMDV2-K16R-PEG28 (2), and (b) IRDye800-PEG28-A20FMDV2-K16R-PEG28 (3). Peptides were synthesized using solid-phase peptide synthesis and standard Fmoc chemistry. Affinity for αvβ6 was evaluated by ELISA. In vitro binding, internalization, and localization of 2 was monitored using confocal microscopy in DX3puroβ6 (αvβ6+) and DX3puro (αvβ6−) cells. The in vivo imaging and ex vivo biodistribution of 3 was evaluated in three preclinical mouse models, DX3puroβ6/DX3puro and BxPC-3 (αvβ6+) tumor xenografts and a BxPC-3 orthotopic pancreatic tumor model. Peptides were obtained in > 99% purity. IC50 values were 28 nM (2) and 39 nM (3). Rapid αvβ6-selective binding and internalization of 2 was observed. Fluorescent intensity (FLI) measurements extracted from the in vivo images and ex vivo biodistribution confirmed uptake and retention of 3 in the αvβ6 positive subcutaneous and orthotopic tumors, with negligible uptake in the αvβ6-negative tumor. Blocking studies with a known αvβ6-targeting peptide demonstrated αvβ6-specific binding of 3. Two fluorescence imaging agents were developed. The αvβ6-specific uptake, internalization, and endosomal localization of the fluorescence agent 2 demonstrates potential for targeted therapy. The selective uptake and retention of 3 in the αvβ6-positive tumors enabled clear delineation of the tumors and surgical resection indicating 3 has the potential to be utilized during image-guided surgery. |
| تدمد: | 1860-2002 1536-1632 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::af6d74009ccc36679a1ca2e2898e6e1e https://doi.org/10.1007/s11307-019-01469-5 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........af6d74009ccc36679a1ca2e2898e6e1e |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 18602002 15361632 |
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