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@ARTICLE{Sinnes:166043,
      author       = {J.-P. Sinnes and U. Bauder-Wüst$^*$ and M. Schäfer$^*$
                      and E. S. Moon and K. Kopka$^*$ and F. Rösch},
      title        = {68{G}a, 44{S}c and 177{L}u-labeled {AAZTA}5-{PSMA}-617:
                      synthesis, radiolabeling, stability and cell binding
                      compared to {DOTA}-{PSMA}-617 analogues.},
      journal      = {EJNMMI radiopharmacy and chemistry},
      volume       = {5},
      number       = {1},
      issn         = {2365-421X},
      address      = {[Heidelberg]},
      publisher    = {SpringerOpen},
      reportid     = {DKFZ-2020-02582},
      pages        = {28},
      year         = {2020},
      abstract     = {The AAZTA chelator and in particular its bifunctional
                      derivative AAZTA5 was recently investigated to demonstrate
                      unique capabilities to complex diagnostic and therapeutic
                      trivalent radiometals under mild conditions. This study
                      presents a comparison of 68Ga, 44Sc and 177Lu-labeled
                      AAZTA5-PSMA-617 with DOTA-PSMA-617 analogues. We evaluated
                      the radiolabeling characteristics, in vitro stability of the
                      radiolabeled compounds and evaluated their binding affinity
                      and internalization behavior on LNCaP tumor cells in direct
                      comparison to the radiolabeled DOTA-conjugated PSMA-617
                      analogs.AAZTA5 was synthesized in a five-step synthesis and
                      coupled to the PSMA-617 backbone on solid phase.
                      Radiochemical evaluation of AAZTA5-PSMA-617 with 68Ga, 44Sc
                      and 177Lu achieved quantitative radiolabeling of > $99\%$
                      after less than 5 min at room temperature. Stabilities
                      against human serum, PBS buffer and EDTA and DTPA solutions
                      were analyzed. While there was a small degradation of the
                      68Ga complex over 2 h in human serum, PBS and EDTA/DTPA, the
                      44Sc and 177Lu complexes were stable at 2 h and remained
                      stable over 8 h and 1 day. For all three compounds, i.e.
                      [natGa]Ga-AAZTA5-PSMA-617, [natSc]Sc-AAZTA5-PSMA-617 and
                      [natLu]Lu-AAZTA5-PSMA-617, in vitro studies on PSMA-positive
                      LNCaP cells were performed in direct comparison to
                      radiolabeled DOTA-PSMA-617 yielding the corresponding
                      inhibition constants (Ki). Ki values were in the range of
                      8-31 nM values which correspond with those of
                      [natGa]Ga-DOTA-PSMA-617, [natSc]Sc-DOTA-PSMA-617 and
                      [natLu]Lu-DOTA-PSMA-617, i.e. 5-7 nM, respectively.
                      Internalization studies demonstrated cellular membrane to
                      internalization ratios for the radiolabeled 68Ga, 44Sc and
                      177Lu-AAZTA5-PSMA-617 tracers $(13-20\%IA/106$ cells) in the
                      same range as the ones of the three radiolabeled
                      DOTA-PSMA-617 tracers $(17-20\%IA/106$ cells) in the same
                      assay.The AAZTA5-PSMA-617 structure proved fast and
                      quantitative radiolabeling with all three radiometal
                      complexes at room temperature, excellent stability with
                      44Sc, very high stability with 177Lu and medium stability
                      with 68Ga in human serum, PBS and EDTA/DTPA solutions. All
                      three AAZTA5-PSMA-617 tracers showed binding affinities and
                      internalization ratios in LNCaP cells comparable with that
                      of radiolabeled DOTA-PSMA-617 analogues. Therefore, the
                      exchange of the chelator DOTA with AAZTA5 within the
                      PSMA-617 binding motif has no negative influence on in vitro
                      LNCaP cell binding characteristics. In combination with the
                      faster and milder radiolabeling features, AAZTA5-PSMA-617
                      thus demonstrates promising potential for in vivo
                      application for theranostics of prostate cancer.},
      cin          = {DD01 / E030},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331 / I:(DE-He78)E030-20160331},
      pnm          = {315 - Imaging and radiooncology (POF3-315)},
      pid          = {G:(DE-HGF)POF3-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33242189},
      doi          = {10.1186/s41181-020-00107-8},
      url          = {https://inrepo02.dkfz.de/record/166043},
}