Comparison of 68Ga-labeled RGD mono- and multimers based on a clickable siderophore-based scaffold
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
PubMed
31678781
DOI
10.1016/j.nucmedbio.2019.09.002
PII: S0969-8051(19)30181-7
Knihovny.cz E-zdroje
- Klíčová slova
- Angiogenesis, Gallium-68, PET, RGD, α(v)β(3) integrin,
- MeSH
- alkyny chemie MeSH
- azidy chemie MeSH
- click chemie MeSH
- cyklické peptidy chemie farmakokinetika MeSH
- izotopové značení MeSH
- měď chemie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- PET/CT MeSH
- polymerizace MeSH
- radioizotopy galia chemie MeSH
- siderofory chemie MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- alkyny MeSH
- azidy MeSH
- cyclic arginine-glycine-aspartic acid peptide MeSH Prohlížeč
- cyklické peptidy MeSH
- Gallium-68 MeSH Prohlížeč
- měď MeSH
- radioizotopy galia MeSH
- siderofory 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
Citace poskytuje Crossref.org
68Ga]Ga-DFO-c(RGDyK): Synthesis and Evaluation of Its Potential for Tumor Imaging in Mice
