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@ARTICLE{Eder:179273,
      author       = {A.-C. Eder$^*$ and J. Matthias and M. Schäfer$^*$ and J.
                      Geberlein$^*$ and N. Steinacker$^*$ and U. Bauder-Wüst$^*$
                      and L.-C. Domogalla$^*$ and M. Roscher$^*$ and U.
                      Haberkorn$^*$ and M. Eder$^*$ and K. Kopka$^*$},
      title        = {{A} {N}ew {C}lass of {PSMA}-617-{B}ased {H}ybrid
                      {M}olecules for {P}reoperative {I}maging and
                      {I}ntraoperative {F}luorescence {N}avigation of {P}rostate
                      {C}ancer.},
      journal      = {Pharmaceuticals},
      volume       = {15},
      number       = {3},
      issn         = {1424-8247},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2022-00555},
      pages        = {267},
      year         = {2022},
      abstract     = {The development of PSMA-targeting low-molecular-weight
                      hybrid molecules aims at advancing preoperative imaging and
                      accurate intraoperative fluorescence guidance for improved
                      diagnosis and therapy of prostate cancer. In hybrid probe
                      design, the major challenge is the introduction of a bulky
                      dye to peptidomimetic core structures without affecting
                      tumor-targeting properties and pharmacokinetic profiles.
                      This study developed a novel class of PSMA-targeting hybrid
                      molecules based on the clinically established theranostic
                      agent PSMA-617. The fluorescent dye-bearing candidates of
                      the strategically designed molecule library were evaluated
                      in in vitro assays based on their PSMA-binding affinity and
                      internalization properties to identify the most favorable
                      hybrid molecule composition for the installation of a bulky
                      dye. The library's best candidate was realized with
                      IRDye800CW providing the lead compound.
                      Glu-urea-Lys-2-Nal-Chx-Lys(IRDye800CW)-DOTA (PSMA-927) was
                      investigated in an in vivo proof-of-concept study, with
                      compelling performance in organ distribution studies,
                      PET/MRI and optical imaging, and with a strong PSMA-specific
                      tumor uptake comparable to that of PSMA-617. This study
                      provides valuable insights about the design of
                      PSMA-targeting low-molecular-weight hybrid molecules, which
                      enable further advances in the field of peptidomimetic
                      hybrid molecule development.},
      keywords     = {PSMA (Other) / guided surgery (Other) / hybrid molecules
                      (Other) / prostate cancer (Other) / theranostics (Other)},
      cin          = {E030 / FR01 / E060 / DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)E030-20160331 / I:(DE-He78)FR01-20160331 /
                      I:(DE-He78)E060-20160331 / I:(DE-He78)DD01-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35337061},
      pmc          = {pmc:PMC8954540},
      doi          = {10.3390/ph15030267},
      url          = {https://inrepo02.dkfz.de/record/179273},
}