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@INPROCEEDINGS{Humpert:1027701,
      author       = {Humpert, Swen and Neumaier, Bernd and Zlatopolskiy, Boris},
      title        = {{C}onvenient preparation of 18{F}-labeled human insulin by
                      {P}d-catalyzed {S}-arylation},
      issn         = {0969-8051},
      reportid     = {FZJ-2024-04011},
      year         = {2022},
      note         = {This work was supported by the DFG grant ZL 65/4-1.},
      abstract     = {Objective: Insulin is a peptide hormone that is produced
                      andsecreted by pancreatic ß-cells. Apart from its
                      well-known role forthe regulation of blood glucose
                      homeostasis, insulin is consideredto be an important
                      modulator of certain brain functions, includingfeeding
                      behavior and cognition, although the mechanisms of insulin
                      transfer into the central nervous system (CNS) remain
                      unclear. Whilethe preparation of several radiolabeled
                      insulin derivatives has beenreported, their application as
                      probes for in vivo PET studies is hamperedby low yields and
                      low molar activities due to inefficient andlengthy
                      production routes. Herein we report a rapid and
                      efficientprocedure for the preparation of high molar
                      activity insulin selectivelylabeled at the Lys29 residue in
                      the B-chain.Methods: Radiolabeling of thiol-modified insulin
                      was performedby S-arylation with
                      2-[18F]Fluoro-5-iodopyridine ([18F]FIPy) in MeCN/phosphate
                      buffer at 37°C for 3 minutes in the presence of XantphosPd
                      G3 catalyst as recently reported [1]. The product was
                      isolated byRP HPLC with a conventional C18 column. The
                      appropriate substratefor S-conjugation was prepared as
                      follows. Treatment of humaninsulin with N-hydroxysuccimidyl
                      ester of S-Trt protected 4-mercaptobutyricacid in DMF/TRIS
                      buffer (pH = 10.5) afforded Lysb29acylated insulin, which
                      was deprotected with TFA/TIS/H2O (75:20:5).[18F]FIPy was
                      prepared from the corresponding DABCO precursorusing the
                      “minimalist” radiofluorination protocol and isolated by
                      SPEor fast HPLC (7 min).Results: Insulin containing an
                      SH-tag at the Lysb29 residue wasprepared in $14\%$ yield
                      over two steps. Subsequent conjugation withSPE-isolated
                      [18F]FIPy afforded the radiolabeled insulin derivative ina
                      RCY of $11\%$ over two steps. In contrast, conjugation of
                      HPLC-isolated[18F]FIPy with only 100–200 nmol
                      thiol-modified insulin yielded thedesired 18F-fluorinated
                      product in RCYs of 35 ± $4\%$ (n=4) with highradiochemical
                      and chemical purity within 60 min. The suitability forin
                      vivo PET studies was exemplified by preparation of 1.2 GBq
                      radiolabeledinsulin with a molar activity of 100 GBq/µmol
                      starting from6 GBq [18F]F−. Conclusion: Highly efficient
                      production of 18F-labeled insulin fromtiny precursor amounts
                      underlines the high potential of Pd-catalyzedS-arylation
                      with [18F]FIPy for radiolabeling of sensitive biomolecules.},
      month         = {May},
      date          = {2022-05-29},
      organization  = {24th International Symposium on
                       Radiopharmaceutical Sciences, Nantes
                       (France), 29 May 2022 - 3 Jun 2022},
      subtyp        = {After Call},
      cin          = {INM-5},
      ddc          = {570},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)6},
      doi          = {10.1016/S0969-8051(22)00259-1},
      url          = {https://juser.fz-juelich.de/record/1027701},
}