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Autor(en) / Beteiligte
Titel
[68Ga]Ga-HBED-CC-FAPI Derivatives with Improved Radiolabeling and Specific Tumor Uptake
Ist Teil von
  • Molecular pharmaceutics, 2023-04, Vol.20 (4), p.2159-2169
Ort / Verlag
United States: American Chemical Society
Erscheinungsjahr
2023
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
  • Fibroblast activation protein (FAP) is selectively expressed in tumors and highly important for maintaining the microenvironment in malignant tumors. Radioisotope-labeled FAP inhibitors (FAPIs) were proven to be useful for diagnosis and radionuclide therapy of cancer and are under active clinical investigations. Ga-HBED complex displays a higher in vivo stability constant (log K GaL: 38.5), compared to that of Ga-DOTA (log K GaL: 21.3). Such advantage in stability constant suggests that it may be useful for development of alternative FAPI imaging agents. In this study, previously reported [68Ga]­Ga-DOTA-FAPI-02 and -04 were converted to the corresponding [68Ga]­Ga-HBED-CC-FAPI-02 and -04 derivatives ([68Ga]­Ga-4, [68Ga]­Ga-5, [68Ga]­Ga-6, and [68Ga]­Ga-7). It was found that substituting the DOTA chelating group with HBED-CC led to several unique and desirable tumor-targeting properties: (1) robust, fast, and high yield labelingreadily adaptable to a kit formulation; (2) high stabilities in vitro; (3) excellent FAP binding affinities (IC50 ranging between 4 and 7 nM) and improved cell uptake and retention (in HT1080 (FAP+) cells); and (4) excellent selective in vivo tumor uptake in nude mice bearing U87MG tumor. It appeared that Ga­(III) chelation with HBED-CC improved the in vivo kinetics favoring higher tumor uptake and retention compared to the corresponding Ga-DOTA complex. Out of the four tested ligands the new [68Ga]­Ga-HBED-CC-FAPI dimer, [68Ga]­Ga-6, displayed the best tumor localization properties, and further studies are warranted to demonstrate that it is an alternative FAP imaging agent for cancer patients.
Sprache
Englisch
Identifikatoren
ISSN: 1543-8384
eISSN: 1543-8392
DOI: 10.1021/acs.molpharmaceut.2c01112
Titel-ID: cdi_proquest_miscellaneous_2789234800

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