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@ARTICLE{Smeets:276748,
      author       = {E. M. M. Smeets and D. N. Dorst and G. M. Franssen and M.
                      S. van Essen and C. Frielink and M. W. J. Stommel and M.
                      Trajkovic-Arsic$^*$ and P. F. Cheung$^*$ and J. Siveke$^*$
                      and I. Wilson and A. Mascioni and E. H. J. G. Aarntzen and
                      S. A. M. van Lith},
      title        = {{F}ibroblast {A}ctivation {P}rotein-{T}argeting
                      {M}inibody-{IRD}ye700{DX} for {A}blation of the
                      {C}ancer-{A}ssociated {F}ibroblast with {P}hotodynamic
                      {T}herapy},
      journal      = {Cells},
      volume       = {12},
      number       = {10},
      issn         = {2073-4409},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-01129},
      pages        = {1420},
      year         = {2023},
      abstract     = {Fibroblast activation protein (FAP), expressed on
                      cancer-associated fibroblasts, is a target for diagnosis and
                      therapy in multiple tumour types. Strategies to systemically
                      deplete FAP-expressing cells show efficacy; however, these
                      induce toxicities, as FAP-expressing cells are found in
                      normal tissues. FAP-targeted photodynamic therapy offers a
                      solution, as it acts only locally and upon activation. Here,
                      a FAP-binding minibody was conjugated to the chelator
                      diethylenetriaminepentaacetic acid (DTPA) and the
                      photosensitizer IRDye700DX (DTPA-700DX-MB). DTPA-700DX-MB
                      showed efficient binding to FAP-overexpressing 3T3 murine
                      fibroblasts (3T3-FAP) and induced the protein’s
                      dose-dependent cytotoxicity upon light exposure.
                      Biodistribution of DTPA-700DX-MB in mice carrying either
                      subcutaneous or orthotopic tumours of murine pancreatic
                      ductal adenocarcinoma cells (PDAC299) showed maximal tumour
                      uptake of 111In-labelled DTPA-700DX-MB at 24 h post
                      injection. Co-injection with an excess DTPA-700DX-MB reduced
                      uptake, and autoradiography correlated with FAP expression
                      in the stromal tumour region. Finally, in vivo therapeutic
                      efficacy was determined in two simultaneous subcutaneous
                      PDAC299 tumours; only one was treated with 690 nm light.
                      Upregulation of an apoptosis marker was only observed in the
                      treated tumours. In conclusion, DTPA-700DX-MB binds to
                      FAP-expressing cells and targets PDAC299 tumours in mice
                      with good signal-to-background ratios. Furthermore, the
                      induced apoptosis indicates the feasibility of targeted
                      depletion of FAP-expressing cells with photodynamic
                      therapy.},
      cin          = {ED01},
      ddc          = {570},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.3390/cells12101420},
      url          = {https://inrepo02.dkfz.de/record/276748},
}