The Effects of an Albumin Binding Moiety on the Targeting and Pharmacokinetics of an Integrin αvβ6-Selective Peptide Labeled with Aluminum [18F]Fluoride
| العنوان: | The Effects of an Albumin Binding Moiety on the Targeting and Pharmacokinetics of an Integrin αvβ6-Selective Peptide Labeled with Aluminum [18F]Fluoride |
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| المؤلفون: | Sarah Y. C. Tang, Tanushree Ganguly, Nadine Bauer, Julie L. Sutcliffe, Ryan A. Davis, Sven H. Hausner |
| المصدر: | Molecular imaging and biology, vol 22, iss 6 |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Integrin alpha(v)beta(6), Fluorine Radioisotopes, Integrins, Cancer Research, Biodistribution, Physiology, Nude, Clinical Sciences, PET imaging, Bioengineering, Peptide, Cell Line, 030218 nuclear medicine & medical imaging, Mice, Fluorides, 03 medical and health sciences, 0302 clinical medicine, In vivo, Cell surface receptor, Albumins, Positron Emission Tomography Computed Tomography, Animals, Moiety, Tissue Distribution, Radiology, Nuclear Medicine and imaging, Chelation, Antigens, Aluminum Compounds, Aluminum [F-18]fluoride, Cancer, chemistry.chemical_classification, Tumor, Chemistry, Albumin, Molecular biology, In vitro, Aluminum [18F]fluoride, Nuclear Medicine & Medical Imaging, Oncology, Integrin αvβ6, Neoplasm, Female, Peptides, Blood circulation, Albumin binding moiety, Protein Binding |
| الوصف: | PurposeThe αvβ6-BP peptide selectively targets the integrin αvβ6, a cell surface receptor recognized as a prognostic indicator for several challenging malignancies. Given that the 4-[18F]fluorobenzoyl (FBA)-labeled peptide is a promising PET imaging agent, radiolabeling via aluminum [18F]fluoride chelation and introduction of an albumin binding moiety (ABM) have the potential to considerably simplify radiochemistry and improve the pharmacokinetics by increasing biological half-life.ProceduresThe peptides NOTA-αvβ6-BP (1) and NOTA-K(ABM)-αvβ6-BP (2) were synthesized on solid phase, radiolabeled with aluminum [18F]fluoride, and evaluated in vitro (integrin ELISA, albumin binding, cell studies) and in vivo in mouse models bearing paired DX3puroβ6 [αvβ6(+)]/DX3puro [αvβ6(-)], and for [18F]AlF 2, BxPC-3 [αvβ6(+)] cell xenografts (PET imaging, biodistribution).ResultsThe peptides were radiolabeled in 23.0 ± 5.7% and 22.1 ± 4.4% decay-corrected radiochemical yield, respectively, for [18F]AlF 1 and [18F]AlF 2. Both demonstrated excellent affinity and selectivity for integrin αvβ6 by ELISA (IC50(αvβ6) = 3-7nM vs IC50(αvβ3) > 10μM) and in cell binding studies (51.0 ± 0.7% and 47.2 ± 0.7% of total radioactivity bound to DX3puroβ6 cells at 1h, respectively, vs. ≤ 1.2% to DX3puro for both compounds). The radiotracer [18F]AlF 1 bound to human serum at 16.3 ± 1.9%, compared to 67.5 ± 1.0% for the ABM-containing [18F]AlF 2. In vivo studies confirmed the effect of the ABM on blood circulation (≤ 0.1% ID/g remaining in blood for [18F]AlF 1 as soon as 1h p.i. vs. > 2% ID/g for [18F]AlF 2 at 6h p.i.) and higher αvβ6(+) tumor uptake (4h: DX3puroβ6; [18F]AlF 1: 3.0 ± 0.7% ID/g, [18F]AlF 2: 7.2 ± 0.7% ID/g; BxPC-3; [18F]AlF 2: 10.2 ± 0.1% ID/g).ConclusionBoth compounds were prepared using standard chemistries; affinity and selectivity for integrin αvβ6 in vitro remained unaffected by the albumin binding moiety. In vivo, the albumin binding moiety resulted in prolonged circulation and higher αvβ6-targeted uptake. |
| وصف الملف: | application/pdf |
| تدمد: | 1860-2002 1536-1632 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f454ee1adb8af73740483e72cb85730e https://doi.org/10.1007/s11307-020-01500-0 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f454ee1adb8af73740483e72cb85730e |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 18602002 15361632 |
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