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@INPROCEEDINGS{Vanasschen:824537,
      author       = {Vanasschen, Christian and Tircsó, Gyula and Monár, Enikő
                      and Brandt, Marie and Ermert, Johannes and Coenen, Heinrich
                      Hubert and Neumaier, Bernd},
      title        = {{A} novel {CDTA}-based bifunctional chelator for
                      52g/55{M}n({II})-labeled bimodal {PET}/{MR} tracers},
      reportid     = {FZJ-2016-07109},
      year         = {2016},
      abstract     = {Research on contrast agents for MRI increasingly
                      concentrates on paramagnetic MnII complexes as alternative
                      to GdIII chelates commonly used in the clinical setting.
                      Besides being an essential metal in vivo and possessing
                      excellent physical properties for T1-weighted MR
                      applications, an additional feature of MnII is the
                      availability of the positron-emitting isotope 52gMn, a
                      promising candidate for PET imaging. We have recently shown
                      that radiolabeling CDTA
                      (trans-1,2-diaminocyclohexane-N,N,N´,N´-tetraacetic acid)
                      with an isotopic 52g/55Mn mixture gives direct access to the
                      corresponding bimodal PET/MR tracer.[1] This technique
                      ensures that both the PET and MR reporter molecules are
                      present in the required concentrations for each imaging
                      modality (PET is >106 times more sensitive than MRI) as well
                      as chemically identical, thus exhibiting the same in vivo
                      behavior.In order to fully benefit from the synergistic
                      combination of PET and MR imaging, a dual modal manganese
                      tracer should either (i) be specific to a tissue/disease,
                      (ii) have a high relaxivity or (iii) be biomarker
                      responsive. As the design of such optimized probes requires
                      the use of a bifunctional MnII chelator (BFMnC), the
                      CuAAC-reactive compound 1 was synthesized in 6 steps with an
                      overall yield of $25\%$ (CuAAC = CuI-catalyzed azide-alkyne
                      cycloaddition). The model chelator 4-HET-CDTA (2), which was
                      obtained by clicking 1 with 2-azidoethanol followed by
                      deprotection, was used to assess the equilibrium and kinetic
                      properties of the corresponding MnII chelate. The stability
                      constant (log KMnL) and the kinetic inertness (characterized
                      by the dissociation half-life, t1/2) obtained for
                      [Mn(4-HET-CDTA)]2- appeared to be equivalent or $35\%$
                      higher, respectively, than for [Mn(CDTA)]2- (see Table).
                      Additionally, the $27\%$ relaxivity increase observed for
                      [Mn(4-HET-CDTA)]2- compared to [Mn(CDTA)]2- indicates that
                      the novel complex is monoaquated (q = 1). Parameter
                      [Mn(4-HET-CDTA)]2- [Mn(CDTA)]2- [2]Stability constant –
                      log KMnL a 13.80 14.32Dissociation half-life – t1/2 (h) b
                      16.23 12.00Relaxivity – r1 (mM-1s-1) c 4.56 3.6Conditions:
                      a = 0.15 M NaCl, 25°C; b pH = 7.4, [Cu2+] = 10-5 M, 25°C;
                      c 20 MHz, 25°C.Current efforts focus on the design of
                      PSMA-targeted 52g/55Mn-tracers for hybrid PET/MR imaging of
                      prostate cancer (PSMA = prostate-specific membrane antigen).
                      Notably, an azide-containing, tert-butyl-protected
                      PSMA-binding motif was prepared and efficiently coupled to
                      BFMnC 1 by CuAAC in $>70\%$ yield. Radiolabeling of the
                      obtained conjugate with isotopic 52g/55Mn upon deprotection
                      is under progress, aiming at the first evaluation of
                      manganese-based PET/MR probes in animal models.},
      month         = {Sep},
      date          = {2016-09-26},
      organization  = {Being Smart In Coordination Chemistry:
                       Medical Applications, Orleans (France),
                       26 Sep 2016 - 28 Sep 2016},
      subtyp        = {Plenary/Keynote},
      cin          = {INM-5},
      cid          = {I:(DE-Juel1)INM-5-20090406},
      pnm          = {573 - Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)24},
      url          = {https://juser.fz-juelich.de/record/824537},
}