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@INPROCEEDINGS{Hoffmann:1026489,
      author       = {Hoffmann, Chris and Gröner, Benedikt and Walter, Nils and
                      Endepols, Heike and Grüll, Holger and Neumaier, Felix and
                      Neumaier, Bernd and Zlatopolskiy, Boris},
      title        = {{P}reparation and preclinical evaluation of novel
                      18{F}-labeled {FAP} ligands},
      reportid     = {FZJ-2024-03433},
      year         = {2023},
      abstract     = {Objectives: Fibroblast activation protein (FAP) is a
                      membraneboundprolyl endopeptidase that is almost exclusively
                      expressed bycancer-associated fibroblasts (CAFs), making it
                      a promising target forpositron emission tomography (PET)
                      imaging of different solid tumors.The aim of this study was
                      the preparation and preclinical evaluation ofthree novel
                      radiofluorinated candidate probes for FAP imaging
                      usingradiolabeling protocols developed in our
                      institute.Methods: [18F]AlF-FAPI-42 ([18F]1) was prepared by
                      chelation of[18F]F– using FAPI-42 precursor (62 nmol) and
                      AlCl3 (30 nmol) inDMSO/50 mM NaOAc buffer (pH 4) mixture
                      (1.4 mL/0.4 mL) at 110 °Cfor 10 min.
                      7-[18F]F-1-Me-2-aza-IA-FAPI ([18F]2) was obtained
                      byconjugation of appropriately modified AMC1110 with
                      7-[18F]F-1-Me-2-aza-IA. The latter was prepared from the
                      respective N,N,N-trimethylammoniumtriflate precursor using
                      (on-cartridge) radiofluorination.6-[18F]F-UAMC1110 ([18F]4)
                      was produced from the respective Me3Snsubstrate (10 μmol)
                      using an optimized protocol for
                      Cu-mediatedradiofluorination, while 6-[18F]FSO2-AMC1110
                      ([18F]3) was preparedby using of an improved procedure for
                      18F/19F SuFEx isotopic exchangefrom 3 (45 nmol). All tracers
                      were purified by HPLC or SPE. The tracercandidates were
                      evaluated by in vivo μPET (120 min emission scanswith a
                      Siemens Focus 220 small animal PET scanner) in
                      immunodeficientSCID mice subcutaneously inoculated with wild
                      type and FAP+transfected HT-1080 cells. The most promising
                      candidate wasadditionally evaluated in a subcutaneous rat
                      model based on the ratpancreatic tumor cell line DSL-6A/C1,
                      which is characterized by apronounced tumor stroma with a
                      high density of cancer-associatedfibroblasts (CAFs).
                      [18F]AlF-FAPI-42 was applied as the reference
                      FAPspecificPET-tracer in all biological experiments.Results:
                      PET probes were prepared as injectable solutions inactivity
                      yields of $25–57\%$ and with molar activities of 28–170
                      GBq/μmol. The in vivo PET measurements demonstrated no
                      accumulation inFAP+-HT-1080 tissue for both [18F]2 and
                      [18F]3, reflecting insufficient ofin vivo stability of
                      [18F]3, and the missing FAP selectivity for [18F]2.
                      Incontrast, [18F]4 demonstrated high accumulation in FAP+
                      tissue andhigh stability in tumor. Uptake of the latter
                      tracer and [18F]1 in FAP+-HT-1080 tumors were comparable and
                      at least twice as high as in wildtype tumors. [18F]4 also
                      enabled a clean delineation of DSL-6A/C1tumors with a
                      target-to-background ratio of about 5, which remainedstable
                      for at least 120 min. In the same model, [18F]1-PET
                      allowedvisualization of tumors with a target-to-background
                      ratio of 10 at40 min p.i., which increased to 15 at 120 min
                      p.i. The higher tumor-tobackgroundratio of [18F]1 was due to
                      lower background activity ratherthan higher tumor uptake.
                      Both [18F]4 and [18F]1 accumulated in galland urinary
                      bladder. [18F]4 showed a particularly strong
                      hepatobiliaryexcretion, resulting in high amounts of
                      radioactivity in the intestinaltract.Conclusions Three novel
                      PET-probes were successfully producedusing emerging
                      radiofluorination methods. Among them [18F]4represents a
                      promising candidate for visualization of FAP-positivetumors.
                      However, it is not superior to [18F]1 because of its
                      higherbackground activity and stronger hepatobiliary
                      excretion.},
      month         = {May},
      date          = {2023-05-22},
      organization  = {25th International Symposium on
                       Radiopharmaceutical Sciences, Honolulu,
                       USA (USA), 22 May 2023 - 26 May 2023},
      subtyp        = {After Call},
      cin          = {INM-5},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)6},
      url          = {https://juser.fz-juelich.de/record/1026489},
}