Molecular Imaging and Preclinical Studies of Radiolabeled Long-Term RGD Peptides in U-87 MG Tumor-Bearing Mice
| Autor: | Chih-Hsien Chang, Wei-Lin Lo, Su-Jung Chen, Liang-Cheng Chen, Yuan-Ruei Huang, Ming-Wei Chen, Ming-Hsin Li, Shih-Wei Lo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Peptide
Mice SCID 030218 nuclear medicine & medical imaging chemistry.chemical_compound Mice 0302 clinical medicine Mice Inbred NOD Tissue Distribution Biology (General) Spectroscopy Evans Blue Chelating Agents chemistry.chemical_classification Indium Radioisotopes General Medicine indium-111 Computer Science Applications Molecular Imaging Chemistry 111In-DOTA-EB-cRGDfK 030220 oncology & carcinogenesis Heterografts Oligopeptides pharmacokinetics Biodistribution QH301-705.5 Peptides Cyclic Catalysis Article Inorganic Chemistry 03 medical and health sciences Heterocyclic Compounds 1-Ring In vivo Cell Line Tumor nanoSPECT/CT DOTA Animals Humans Physical and Theoretical Chemistry Molecular Biology neoplasms QD1-999 Organic Chemistry Molecular biology In vitro Rats chemistry Radionuclide therapy Cancer cell Radiopharmaceuticals Glioblastoma |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 5459, p 5459 (2021) International Journal of Molecular Sciences Volume 22 Issue 11 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | The Arg–Gly–Asp (RGD) peptide shows a high affinity for αvβ3 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(111In) radiolabeled DOTA-EB-cRGDfK in αvβ3 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 111In-DOTA-EB-cRGDfK had a significant binding affinity to U-87 MG cancer cells (IC50 = 71.7 nM). NanoSPECT/CT imaging showed 111In-DOTA-EB-cRGDfK has higher tumor uptake than control peptides (111In-DOTA-cRGDfK and 111In-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 111In-DOTA-EB-cRGDfK peptide has a long-term half-life (T1/2λz = 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. |
| Databáze: | OpenAIRE |
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