A Comparison of Evans Blue and 4-(<i>p</i>-Iodophenyl)butyryl Albumin Binding Moieties on an Integrin α<sub>v</sub>β<sub>6</sub> Binding Peptide
Serum albumin binding moieties (ABMs) such as the Evans blue (EB) dye fragment and the 4-(<i>p</i>-iodophenyl)butyryl (IP) have been used to improve the pharmacokinetic profile of many radiopharmaceuticals. The goal of this work was to directly compare these two ABMs when conjugated to a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/4/745 |
| _version_ | 1797444249141116928 |
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| author | Ryan A. Davis Sven H. Hausner Rebecca Harris Julie L. Sutcliffe |
| author_facet | Ryan A. Davis Sven H. Hausner Rebecca Harris Julie L. Sutcliffe |
| author_sort | Ryan A. Davis |
| collection | DOAJ |
| description | Serum albumin binding moieties (ABMs) such as the Evans blue (EB) dye fragment and the 4-(<i>p</i>-iodophenyl)butyryl (IP) have been used to improve the pharmacokinetic profile of many radiopharmaceuticals. The goal of this work was to directly compare these two ABMs when conjugated to an integrin α<sub>v</sub>β<sub>6</sub> binding peptide (α<sub>v</sub>β<sub>6</sub>-BP); a peptide that is currently being used for positron emission tomography (PET) imaging in patients with metastatic cancer. The ABM-modified α<sub>v</sub>β<sub>6</sub>-BP peptides were synthesized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA) chelator for radiolabeling with copper-64 to yield [<sup>64</sup>Cu]Cu DOTA-EB-α<sub>v</sub>β<sub>6</sub>-BP ([<sup>64</sup>Cu]<b>1</b>) and [<sup>64</sup>Cu]Cu DOTA-IP-α<sub>v</sub>β<sub>6</sub>-BP ([<sup>64</sup>Cu]<b>2</b>). Both peptides were evaluated in vitro for serum albumin binding, serum stability, and cell binding and internalization in the paired engineered melanoma cells DX3puroβ6 (α<sub>v</sub>β<sub>6</sub> +) and DX3puro (α<sub>v</sub>β<sub>6</sub> −), and pancreatic BxPC-3 (α<sub>v</sub>β<sub>6</sub> +) cells and in vivo in a BxPC-3 xenograft mouse model. Serum albumin binding for [<sup>64</sup>Cu]<b>1</b> and [<sup>64</sup>Cu]<b>2</b> was 53–63% and 42–44%, respectively, with good human serum stability (24 h: [<sup>64</sup>Cu]<b>1</b> 76%, [<sup>64</sup>Cu]<b>2</b> 90%). Selective α<sub>v</sub>β<sub>6</sub> cell binding was observed for both [<sup>64</sup>Cu]<b>1</b> and [<sup>64</sup>Cu]<b>2</b> (α<sub>v</sub>β<sub>6</sub> (+) cells: 30.3–55.8% and 48.5–60.2%, respectively, vs. α<sub>v</sub>β<sub>6</sub> (−) cells <3.1% for both). In vivo BxPC-3 tumor uptake for both peptides at 4 h was 5.29 ± 0.59 and 7.60 ± 0.43% ID/g ([<sup>64</sup>Cu]<b>1</b> and [<sup>64</sup>Cu]<b>2</b>, respectively), and remained at 3.32 ± 0.46 and 4.91 ± 1.19% ID/g, respectively, at 72 h, representing a >3-fold improvement over the non-ABM parent peptide and thereby providing improved PET images. Comparing [<sup>64</sup>Cu]<b>1</b> and [<sup>64</sup>Cu]<b>2</b>, the IP-ABM-α<sub>v</sub>β<sub>6</sub>-BP [<sup>64</sup>Cu]<b>2</b> displayed higher serum stability, higher tumor accumulation, and lower kidney and liver accumulation, resulting in better tumor-to-organ ratios for high contrast visualization of the α<sub>v</sub>β<sub>6</sub> (+) tumor by PET imaging. |
| first_indexed | 2024-03-09T13:09:52Z |
| format | Article |
| id | doaj.art-ab89510f9ce1449c961c8aa27dc4f78f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T13:09:52Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-ab89510f9ce1449c961c8aa27dc4f78f2023-11-30T21:43:52ZengMDPI AGPharmaceutics1999-49232022-03-0114474510.3390/pharmaceutics14040745A Comparison of Evans Blue and 4-(<i>p</i>-Iodophenyl)butyryl Albumin Binding Moieties on an Integrin α<sub>v</sub>β<sub>6</sub> Binding PeptideRyan A. Davis0Sven H. Hausner1Rebecca Harris2Julie L. Sutcliffe3Department of Biomedical Engineering, University of California, Davis, CA 95616, USADepartment of Internal Medicine, Division of Hematology/Oncology, University of California, Davis, CA 95817, USADepartment of Internal Medicine, Division of Hematology/Oncology, University of California, Davis, CA 95817, USADepartment of Biomedical Engineering, University of California, Davis, CA 95616, USASerum albumin binding moieties (ABMs) such as the Evans blue (EB) dye fragment and the 4-(<i>p</i>-iodophenyl)butyryl (IP) have been used to improve the pharmacokinetic profile of many radiopharmaceuticals. The goal of this work was to directly compare these two ABMs when conjugated to an integrin α<sub>v</sub>β<sub>6</sub> binding peptide (α<sub>v</sub>β<sub>6</sub>-BP); a peptide that is currently being used for positron emission tomography (PET) imaging in patients with metastatic cancer. The ABM-modified α<sub>v</sub>β<sub>6</sub>-BP peptides were synthesized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA) chelator for radiolabeling with copper-64 to yield [<sup>64</sup>Cu]Cu DOTA-EB-α<sub>v</sub>β<sub>6</sub>-BP ([<sup>64</sup>Cu]<b>1</b>) and [<sup>64</sup>Cu]Cu DOTA-IP-α<sub>v</sub>β<sub>6</sub>-BP ([<sup>64</sup>Cu]<b>2</b>). Both peptides were evaluated in vitro for serum albumin binding, serum stability, and cell binding and internalization in the paired engineered melanoma cells DX3puroβ6 (α<sub>v</sub>β<sub>6</sub> +) and DX3puro (α<sub>v</sub>β<sub>6</sub> −), and pancreatic BxPC-3 (α<sub>v</sub>β<sub>6</sub> +) cells and in vivo in a BxPC-3 xenograft mouse model. Serum albumin binding for [<sup>64</sup>Cu]<b>1</b> and [<sup>64</sup>Cu]<b>2</b> was 53–63% and 42–44%, respectively, with good human serum stability (24 h: [<sup>64</sup>Cu]<b>1</b> 76%, [<sup>64</sup>Cu]<b>2</b> 90%). Selective α<sub>v</sub>β<sub>6</sub> cell binding was observed for both [<sup>64</sup>Cu]<b>1</b> and [<sup>64</sup>Cu]<b>2</b> (α<sub>v</sub>β<sub>6</sub> (+) cells: 30.3–55.8% and 48.5–60.2%, respectively, vs. α<sub>v</sub>β<sub>6</sub> (−) cells <3.1% for both). In vivo BxPC-3 tumor uptake for both peptides at 4 h was 5.29 ± 0.59 and 7.60 ± 0.43% ID/g ([<sup>64</sup>Cu]<b>1</b> and [<sup>64</sup>Cu]<b>2</b>, respectively), and remained at 3.32 ± 0.46 and 4.91 ± 1.19% ID/g, respectively, at 72 h, representing a >3-fold improvement over the non-ABM parent peptide and thereby providing improved PET images. Comparing [<sup>64</sup>Cu]<b>1</b> and [<sup>64</sup>Cu]<b>2</b>, the IP-ABM-α<sub>v</sub>β<sub>6</sub>-BP [<sup>64</sup>Cu]<b>2</b> displayed higher serum stability, higher tumor accumulation, and lower kidney and liver accumulation, resulting in better tumor-to-organ ratios for high contrast visualization of the α<sub>v</sub>β<sub>6</sub> (+) tumor by PET imaging.https://www.mdpi.com/1999-4923/14/4/745albumin binding moietiespeptidesEvans blue4-(<i>p</i>-iodophenyl)butyric acidintegrin α<sub>v</sub>β<sub>6</sub>integrin α<sub>v</sub>β<sub>6</sub> binding peptide |
| spellingShingle | Ryan A. Davis Sven H. Hausner Rebecca Harris Julie L. Sutcliffe A Comparison of Evans Blue and 4-(<i>p</i>-Iodophenyl)butyryl Albumin Binding Moieties on an Integrin α<sub>v</sub>β<sub>6</sub> Binding Peptide Pharmaceutics albumin binding moieties peptides Evans blue 4-(<i>p</i>-iodophenyl)butyric acid integrin α<sub>v</sub>β<sub>6</sub> integrin α<sub>v</sub>β<sub>6</sub> binding peptide |
| title | A Comparison of Evans Blue and 4-(<i>p</i>-Iodophenyl)butyryl Albumin Binding Moieties on an Integrin α<sub>v</sub>β<sub>6</sub> Binding Peptide |
| title_full | A Comparison of Evans Blue and 4-(<i>p</i>-Iodophenyl)butyryl Albumin Binding Moieties on an Integrin α<sub>v</sub>β<sub>6</sub> Binding Peptide |
| title_fullStr | A Comparison of Evans Blue and 4-(<i>p</i>-Iodophenyl)butyryl Albumin Binding Moieties on an Integrin α<sub>v</sub>β<sub>6</sub> Binding Peptide |
| title_full_unstemmed | A Comparison of Evans Blue and 4-(<i>p</i>-Iodophenyl)butyryl Albumin Binding Moieties on an Integrin α<sub>v</sub>β<sub>6</sub> Binding Peptide |
| title_short | A Comparison of Evans Blue and 4-(<i>p</i>-Iodophenyl)butyryl Albumin Binding Moieties on an Integrin α<sub>v</sub>β<sub>6</sub> Binding Peptide |
| title_sort | comparison of evans blue and 4 i p i iodophenyl butyryl albumin binding moieties on an integrin α sub v sub β sub 6 sub binding peptide |
| topic | albumin binding moieties peptides Evans blue 4-(<i>p</i>-iodophenyl)butyric acid integrin α<sub>v</sub>β<sub>6</sub> integrin α<sub>v</sub>β<sub>6</sub> binding peptide |
| url | https://www.mdpi.com/1999-4923/14/4/745 |
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