FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2117793166> ?p ?o ?g. }

• W2117793166 endingPage "632" @default.
• W2117793166 startingPage "618" @default.
• W2117793166 abstract "The correlation between uPAR expression, cancer cell invasion and metastases is now well-established and has prompted the development of a number of uPAR PET imaging agents, which could potentially identify cancer patients with invasive and metastatic lesions. In the present study, we synthesized and characterized two new cross-bridged (64)Cu-labeled peptide conjugates for PET imaging of uPAR and performed a head-to-head comparison with the corresponding and more conventionally used DOTA conjugate. Based on in-source laser-induced reduction of chelated Cu(II) to Cu(I), we now demonstrate the following ranking with respect to the chemical inertness of their complexed Cu ions: DOTA-AE105 << CB-TE2A-AE105 < CB-TE2A-PA-AE105, which is correlated to their corresponding demetallation rate. No penalty in the uPAR receptor binding affinity of the targeting peptide was encountered by conjugation to either of the macrobicyclic chelators (IC50 ~ 5-10 nM) and high yields and radiochemical purities (>95%) were achieved in all cases by incubation at 95ºC. In vivo, they display identical tumor uptake after 1h, but differ significantly after 22 hrs, where the DOTA-AE105 uptake remains surprisingly high. Importantly, the more stable of the new uPAR PET tracers, (64)Cu-CB-TE2A-PA-AE105, exhibits a significantly reduced liver uptake compared to (64)Cu-DOTA-AE105 as well as (64)Cu-CB-TE2A-AE105, (p<0.0001), emphasizing that our new in vitro stability measurements by mass spectrometry predicts in vivo stability in mice. Specificity of the best performing ligand, (64)Cu-CB-TE2A-PA-AE105 was finally confirmed in vivo using a non-binding (64)Cu-labeled peptide as control ((64)Cu-CB-TE2A-PA-AE105(mut)). This control PET-tracer revealed significantly reduced tumor uptake (p<0.0001), but identical hepatic uptake compared to its active counterpart ((64)Cu-CB-TE2A-PA-AE105) after 1h. In conclusion, our new approach using in-source laser-induced reduction of Cu(II)-chelated PET-ligands provides useful information, which are predictive for the tracer stability in vivo in mice. Furthermore, the increased stability of our new macrobicyclic (64)Cu-CB-TE2A-PA-AE105 PET ligand is paralleled by an excellent imaging contrast during non-invasive PET scanning of uPAR expression in preclinical mouse cancer models. The translational promises displayed by this PET-tracer for future clinical cancer patient management remains, however, to be investigated." @default.
• W2117793166 created "2016-06-24" @default.
• W2117793166 creator A5012570344 @default.
• W2117793166 creator A5044660787 @default.
• W2117793166 creator A5053745370 @default.
• W2117793166 creator A5066094184 @default.
• W2117793166 creator A5071117617 @default.
• W2117793166 creator A5071426519 @default.
• W2117793166 creator A5089128595 @default.
• W2117793166 date "2013-01-01" @default.
• W2117793166 modified "2023-10-17" @default.
• W2117793166 title "Improved PET Imaging of uPAR Expression Using new ⁶⁴Cu-labeled Cross-Bridged Peptide Ligands: Comparative <i>in vitro</i> and <i>in vivo</i> Studies" @default.
• W2117793166 cites W101610969 @default.
• W2117793166 cites W1611413521 @default.
• W2117793166 cites W1967535688 @default.
• W2117793166 cites W1971358567 @default.
• W2117793166 cites W1973717257 @default.
• W2117793166 cites W1974687417 @default.
• W2117793166 cites W1981942027 @default.
• W2117793166 cites W1993945278 @default.
• W2117793166 cites W1995198080 @default.
• W2117793166 cites W1998927810 @default.
• W2117793166 cites W2000171543 @default.
• W2117793166 cites W2001207474 @default.
• W2117793166 cites W2001335554 @default.
• W2117793166 cites W2003844587 @default.
• W2117793166 cites W2005389389 @default.
• W2117793166 cites W2005490647 @default.
• W2117793166 cites W2006054202 @default.
• W2117793166 cites W2012080977 @default.
• W2117793166 cites W2022349358 @default.
• W2117793166 cites W2022381933 @default.
• W2117793166 cites W2023687344 @default.
• W2117793166 cites W2031633375 @default.
• W2117793166 cites W2033466592 @default.
• W2117793166 cites W2044356243 @default.
• W2117793166 cites W2046214723 @default.
• W2117793166 cites W2057938042 @default.
• W2117793166 cites W2061339970 @default.
• W2117793166 cites W2062695451 @default.
• W2117793166 cites W2068678479 @default.
• W2117793166 cites W2070016082 @default.
• W2117793166 cites W2073633749 @default.
• W2117793166 cites W2073864312 @default.
• W2117793166 cites W2075266722 @default.
• W2117793166 cites W2080792219 @default.
• W2117793166 cites W2084888085 @default.
• W2117793166 cites W2092780067 @default.
• W2117793166 cites W2094348788 @default.
• W2117793166 cites W2095734930 @default.
• W2117793166 cites W2105230577 @default.
• W2117793166 cites W2113364712 @default.
• W2117793166 cites W2123271095 @default.
• W2117793166 cites W2127160878 @default.
• W2117793166 cites W2142252428 @default.
• W2117793166 cites W2143415621 @default.
• W2117793166 cites W2143686200 @default.
• W2117793166 cites W2144862049 @default.
• W2117793166 cites W2148864767 @default.
• W2117793166 cites W2151328170 @default.
• W2117793166 cites W2152391708 @default.
• W2117793166 cites W2154506800 @default.
• W2117793166 cites W2166796054 @default.
• W2117793166 cites W2167077736 @default.
• W2117793166 cites W235437893 @default.
• W2117793166 cites W2355629516 @default.
• W2117793166 doi "https://doi.org/10.7150/thno.6810" @default.
• W2117793166 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3776215" @default.
• W2117793166 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24052804" @default.
• W2117793166 hasPublicationYear "2013" @default.
• W2117793166 type Work @default.
• W2117793166 sameAs 2117793166 @default.
• W2117793166 citedByCount "49" @default.
• W2117793166 countsByYear W21177931662014 @default.
• W2117793166 countsByYear W21177931662015 @default.
• W2117793166 countsByYear W21177931662016 @default.
• W2117793166 countsByYear W21177931662017 @default.
• W2117793166 countsByYear W21177931662018 @default.
• W2117793166 countsByYear W21177931662019 @default.
• W2117793166 countsByYear W21177931662020 @default.
• W2117793166 countsByYear W21177931662021 @default.
• W2117793166 countsByYear W21177931662022 @default.
• W2117793166 countsByYear W21177931662023 @default.
• W2117793166 crossrefType "journal-article" @default.
• W2117793166 hasAuthorship W2117793166A5012570344 @default.
• W2117793166 hasAuthorship W2117793166A5044660787 @default.
• W2117793166 hasAuthorship W2117793166A5053745370 @default.
• W2117793166 hasAuthorship W2117793166A5066094184 @default.
• W2117793166 hasAuthorship W2117793166A5071117617 @default.
• W2117793166 hasAuthorship W2117793166A5071426519 @default.
• W2117793166 hasAuthorship W2117793166A5089128595 @default.
• W2117793166 hasBestOaLocation W21177931661 @default.
• W2117793166 hasConcept C116569031 @default.
• W2117793166 hasConcept C134306372 @default.
• W2117793166 hasConcept C136339569 @default.
• W2117793166 hasConcept C150903083 @default.
• W2117793166 hasConcept C153911025 @default.
• W2117793166 hasConcept C170493617 @default.

• next