Comparison of 68Ga-labeled RGD mono- and multimers based on a clickable siderophore-based scaffold
Language English Country United States Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
31678781
DOI
10.1016/j.nucmedbio.2019.09.002
PII: S0969-8051(19)30181-7
Knihovny.cz E-resources
- Keywords
- Angiogenesis, Gallium-68, PET, RGD, α(v)β(3) integrin,
- MeSH
- Alkynes chemistry MeSH
- Azides chemistry MeSH
- Click Chemistry MeSH
- Peptides, Cyclic chemistry pharmacokinetics MeSH
- Isotope Labeling MeSH
- Copper chemistry MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Positron Emission Tomography Computed Tomography MeSH
- Polymerization MeSH
- Gallium Radioisotopes chemistry MeSH
- Siderophores chemistry MeSH
- Tissue Distribution MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Alkynes MeSH
- Azides MeSH
- cyclic arginine-glycine-aspartic acid peptide MeSH Browser
- Peptides, Cyclic MeSH
- Gallium-68 MeSH Browser
- Copper MeSH
- Gallium Radioisotopes MeSH
- Siderophores MeSH
Cyclic pentapeptides containing the amino acid sequence arginine-glycine-aspartic (RGD) have been widely applied to target αvβ3 integrin, which is upregulated in various tumors during tumor-induced angiogenesis. Multimeric cyclic RGD peptides have been reported to be advantageous over monomeric counterparts for angiogenesis imaging. Here, we prepared mono-, di-, and trimeric cyclic arginine-glycine-aspartic-D-phenylalanine-lysine (c (RGDfK)) derivatives by conjugation with the natural chelator fusarinine C (FSC) using click chemistry based on copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC). The αvβ3 binding properties of 68Ga-labeled mono-, di-, and trimeric c(RGDfK) peptides were evaluated in vitro as well as in vivo and compared with the references monomeric [68Ga]GaNODAGA-c(RGDfK) and trimeric [68Ga]GaFSC(suc-c(RGDfK))3. All 68Ga-labeled c(RGDfK) peptides displayed hydrophilicity (logD = -2.96 to -3.80), low protein binding and were stable in phosphate buffered-saline (PBS) and serum up to 2 h. In vitro internalization assays with human melanoma M21 (αvβ3-positive) and M21-L (αvβ3-negative) cell lines showed specific uptake of all derivatives and increased in the series: mono- < di- < trimeric peptide. The highest tumor uptake, tumor-to-background ratios, and image contrast were found for the dimeric [68Ga]GaMAFC(c(RGDfK)aza)2. In conclusion, we developed a novel strategy for direct, straight forward preparation of mono-, di-, and trimeric c(RGDfK) conjugates based on the FSC scaffold. Interestingly, the best αvβ3 imaging properties were found for the dimeric [68Ga]GaMAFC(c(RGDfK)aza)2.
Department of Nuclear Medicine Medical University Innsbruck Innsbruck Austria
Division of Molecular Biology Biocenter Medical University Innsbruck Innsbruck Austria
References provided by Crossref.org
68Ga]Ga-DFO-c(RGDyK): Synthesis and Evaluation of Its Potential for Tumor Imaging in Mice
