Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice
The Arg–Gly–Asp (RGD) peptide shows a high affinity for α<sub>v</sub>β<sub>3</sub> integrin, which is overexpressed in new tumor blood vessels and many types of tumor cells. The radiolabeled RGD peptide has been studied for cancer imaging and radionuclide therapy. We have dev...
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MDPI AG
2021-05-01
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/5459 |
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| author | Wei-Lin Lo Shih-Wei Lo Su-Jung Chen Ming-Wei Chen Yuan-Ruei Huang Liang-Cheng Chen Chih-Hsien Chang Ming-Hsin Li |
| author_facet | Wei-Lin Lo Shih-Wei Lo Su-Jung Chen Ming-Wei Chen Yuan-Ruei Huang Liang-Cheng Chen Chih-Hsien Chang Ming-Hsin Li |
| author_sort | Wei-Lin Lo |
| collection | DOAJ |
| description | The Arg–Gly–Asp (RGD) peptide shows a high affinity for α<sub>v</sub>β<sub>3</sub> integrin, which is overexpressed in new tumor blood vessels and many types of tumor cells. The radiolabeled RGD peptide has been studied for cancer imaging and radionuclide therapy. We have developed a long-term tumor-targeting peptide DOTA-EB-cRGDfK, which combines a DOTA chelator, a truncated Evans blue dye (EB), a modified linker, and cRGDfK peptide. The aim of this study was to evaluate the potential of indium-111(<sup>111</sup>In) radiolabeled DOTA-EB-cRGDfK in α<sub>v</sub>β<sub>3</sub> integrin-expressing tumors. The human glioblastoma cell line U-87 MG was used to determine the in vitro binding affinity of the radiolabeled peptide. The in vivo distribution of radiolabeled peptides in U-87 MG xenografts was investigated by biodistribution, nanoSPECT/CT, pharmacokinetic and excretion studies. The in vitro competition assay showed that <sup>111</sup>In-DOTA-EB-cRGDfK had a significant binding affinity to U-87 MG cancer cells (IC<sub>50</sub> = 71.7 nM). NanoSPECT/CT imaging showed <sup>111</sup>In-DOTA-EB-cRGDfK has higher tumor uptake than control peptides (<sup>111</sup>In-DOTA-cRGDfK and <sup>111</sup>In-DOTA-EB), and there is still a clear signal until 72 h after injection. The biodistribution results showed significant tumor accumulation (27.1 ± 2.7% ID/g) and the tumor to non-tumor ratio was 22.85 at 24 h after injection. In addition, the pharmacokinetics results indicated that the <sup>111</sup>In-DOTA-EB-cRGDfK peptide has a long-term half-life (T<sub>1/2</sub><sub>λ</sub><sub>z</sub> = 77.3 h) and that the calculated absorbed dose was safe for humans. We demonstrated that radiolabeled DOTA-EB-cRGDfK may be a promising agent for glioblastoma tumor imaging and has the potential as a theranostic radiopharmaceutical. |
| first_indexed | 2024-03-10T11:09:12Z |
| format | Article |
| id | doaj.art-4aaa7a8f5b834797a5e4794fb75f4980 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:09:12Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-4aaa7a8f5b834797a5e4794fb75f49802023-11-21T20:52:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211545910.3390/ijms22115459Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing MiceWei-Lin Lo0Shih-Wei Lo1Su-Jung Chen2Ming-Wei Chen3Yuan-Ruei Huang4Liang-Cheng Chen5Chih-Hsien Chang6Ming-Hsin Li7Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan 32546, TaiwanDivision of Isotope Application, Institute of Nuclear Energy Research, Taoyuan 32546, TaiwanDivision of Isotope Application, Institute of Nuclear Energy Research, Taoyuan 32546, TaiwanDivision of Isotope Application, Institute of Nuclear Energy Research, Taoyuan 32546, TaiwanDivision of Isotope Application, Institute of Nuclear Energy Research, Taoyuan 32546, TaiwanDivision of Isotope Application, Institute of Nuclear Energy Research, Taoyuan 32546, TaiwanDivision of Isotope Application, Institute of Nuclear Energy Research, Taoyuan 32546, TaiwanDivision of Isotope Application, Institute of Nuclear Energy Research, Taoyuan 32546, TaiwanThe Arg–Gly–Asp (RGD) peptide shows a high affinity for α<sub>v</sub>β<sub>3</sub> integrin, which is overexpressed in new tumor blood vessels and many types of tumor cells. The radiolabeled RGD peptide has been studied for cancer imaging and radionuclide therapy. We have developed a long-term tumor-targeting peptide DOTA-EB-cRGDfK, which combines a DOTA chelator, a truncated Evans blue dye (EB), a modified linker, and cRGDfK peptide. The aim of this study was to evaluate the potential of indium-111(<sup>111</sup>In) radiolabeled DOTA-EB-cRGDfK in α<sub>v</sub>β<sub>3</sub> integrin-expressing tumors. The human glioblastoma cell line U-87 MG was used to determine the in vitro binding affinity of the radiolabeled peptide. The in vivo distribution of radiolabeled peptides in U-87 MG xenografts was investigated by biodistribution, nanoSPECT/CT, pharmacokinetic and excretion studies. The in vitro competition assay showed that <sup>111</sup>In-DOTA-EB-cRGDfK had a significant binding affinity to U-87 MG cancer cells (IC<sub>50</sub> = 71.7 nM). NanoSPECT/CT imaging showed <sup>111</sup>In-DOTA-EB-cRGDfK has higher tumor uptake than control peptides (<sup>111</sup>In-DOTA-cRGDfK and <sup>111</sup>In-DOTA-EB), and there is still a clear signal until 72 h after injection. The biodistribution results showed significant tumor accumulation (27.1 ± 2.7% ID/g) and the tumor to non-tumor ratio was 22.85 at 24 h after injection. In addition, the pharmacokinetics results indicated that the <sup>111</sup>In-DOTA-EB-cRGDfK peptide has a long-term half-life (T<sub>1/2</sub><sub>λ</sub><sub>z</sub> = 77.3 h) and that the calculated absorbed dose was safe for humans. We demonstrated that radiolabeled DOTA-EB-cRGDfK may be a promising agent for glioblastoma tumor imaging and has the potential as a theranostic radiopharmaceutical.https://www.mdpi.com/1422-0067/22/11/5459<sup>111</sup>In-DOTA-EB-cRGDfKindium-111nanoSPECT/CTpharmacokinetics |
| spellingShingle | Wei-Lin Lo Shih-Wei Lo Su-Jung Chen Ming-Wei Chen Yuan-Ruei Huang Liang-Cheng Chen Chih-Hsien Chang Ming-Hsin Li Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice International Journal of Molecular Sciences <sup>111</sup>In-DOTA-EB-cRGDfK indium-111 nanoSPECT/CT pharmacokinetics |
| title | Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice |
| title_full | Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice |
| title_fullStr | Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice |
| title_full_unstemmed | Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice |
| title_short | Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice |
| title_sort | molecular imaging and preclinical studies of radiolabeled long term rgd peptides in u 87 mg tumor bearing mice |
| topic | <sup>111</sup>In-DOTA-EB-cRGDfK indium-111 nanoSPECT/CT pharmacokinetics |
| url | https://www.mdpi.com/1422-0067/22/11/5459 |
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