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@INPROCEEDINGS{Strecker:1027702,
      author       = {Strecker, Jonas and Spahn, Ingo and Neumaier, Bernd and
                      Giesen, Kai and Gülez, Salim},
      title        = {52g{M}n({II})-{L}abelled {PSMA}-ligands as bimodal
                      {PET}/{MR} imaging probes},
      issn         = {0969-8051},
      reportid     = {FZJ-2024-04012},
      year         = {2022},
      abstract     = {Introduction: By combining the advantages of two or more
                      complementaryimaging modalities, hybrid techniques like
                      PET/MR allowfor sequential or simultaneous acquisition of
                      anatomical and molecularinformation. Although the alignment
                      of hybrid datasets acquiredin simultaneous PET/MR has been
                      shown to be more accurate, thereis still a lack of probes
                      for bimodal PET/MR imaging. Radiolabellingwith isotopic
                      mixtures of 52gMn/55Mn provides direct access to
                      suchprobes1,2, as the paramagnetic 55Mn acts as an MRI
                      contrast agent3,while 52gMn is a promising +-emitter for
                      PET imaging (t½ = 5.6 d, E+,end = 0,58 MeV). In the
                      present work, the PSMA-selective moiety Glu-C(O)-Lys was
                      functionalized by CuAAC click reaction with the
                      chelatortrans-1,2-diaminocyclohexane-N,N,N`,N`-tetraacetic
                      acid (CDTA)for Mn complexation and radiolabeling with 52gMn.
                      In addition, thestability of the novel PET/MR probe was
                      evaluated by preliminary invitro studies.Materials and
                      Methods: Following its production by the52Cr(p,n)52gMn
                      nuclear reaction, 52gMn was separated from the Crtarget
                      using anion exchange chromatography. To this end, the
                      Crtarget was dissolved in 2 m HCl, which was then evaporated
                      todryness. The residue was dissolved in MeOH/conc. HAc (1:1)
                      andtrapped on an AG-MP1 anion exchange column. The column
                      waswashed with 30 mL MeOH/conc. HAc. (1:1) at 44°C and
                      [52gMn]MnCl2was eluted with 3 m HCl.The CDTA ligand was
                      synthesized using a modification of a previouslypublished
                      method4 and coupled to the PSMA-selective Glu-C(O)-Lys
                      pharmacophore by the copper(I)-catalyzed
                      alkyne-azidecycloaddition (CuAAC) click reaction.The
                      functionalized CDTA-ligand (2.5 mg) was dissolved in 0.1
                      mNaOAc buffer (pH 6) and treated with no-carrier added
                      [52gMn]MnCl2for 30 min at ambient temperature, and the
                      radiolabelled productwas subsequently isolated by HPLC.The
                      stability of the PET/MR probe in the presence of human
                      serumwas measured in HBS buffer at 37°C and analysed by
                      HPLC.Results and Conclusion: No-carrier added 52gMn was
                      isolatedfrom the Cr target with a separation yield of
                      $93\%.$ An improved labellingprotocol for the CDTA
                      functionalized PSMA-selective ligand wasestablished,
                      yielding a radiochemical yield of 50 $\%$ (based on
                      HPLCanalysis of the crude product). After 24 h, $28.2\%$ of
                      the complex wasstill intact justifying further evaluation by
                      in vivo animal studies.References:[1] Thomas G. et al.
                      Innovative Magnetic Nanoparticles for PET/MRIBimodal
                      Imaging. ACS Omega. 2019, 4, 2637-2648[2] de Rosales R.T.M.
                      Potential clinical applications of bimodalPET-MRI or
                      SPECT-MRI agents J. Label Compd. Radiopharm. 2014,57,
                      298–303[3] Glover, P., Mansfield, S. P. Limits to magnetic
                      resonance microscopy.Reports Prog. Phys. 2002, 65, 1489.[4]
                      Vanasschen, C., Brandt, M., Ermert, J., Coenen, H. H.
                      Radiolabellingwith isotopic mixtures of 52g/55Mn(II) as a
                      straight route to stablemanganese complexes for bimodal
                      PET/MR imaging. Dalt. Trans.2016, 45, 1315–1321.},
      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)00335-3},
      url          = {https://juser.fz-juelich.de/record/1027702},
}