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@INPROCEEDINGS{Petina:824536,
      author       = {Petina, Olga and Ermert, Johannes and Coenen, Heinrich
                      Hubert and Neumaier, Bernd},
      title        = {{NOTA}- and {DOTA}-coated gold nanoparticles for bimodal
                      {PET}-{MR} molecular imaging},
      reportid     = {FZJ-2016-07108},
      year         = {2016},
      abstract     = {Bimodal hybrid PET-MR imaging offers as valuable and
                      promising tool for non-invasive diagnosis ofvarious diseases
                      as it benefits from the advantages of both individual
                      imaging modalities, i.e. thesuperb soft tissue contrast of
                      MRI combined with the excellent sensitivity and ability of
                      quantificationof PET. With hybrid PET-MR scanners already
                      available, the development of suitable bimodal PET-MRimaging
                      agents is essential. Those molecular probes will provide
                      better morphological correlation ofmolecular function,
                      biomarker-responsive imaging and time-saving
                      “PET-guided” high-resolutionMRI.For this purpose, gold
                      nanoparticle (Au-NP) based bimodal contrast agents were
                      designed. Incontrast to small organic molecules with a
                      limited number of attachment points, nanoparticles (NPs)can
                      be loaded with various ligands in the required ratio. This
                      allows to overcome the mismatch ofconcentrations of the
                      imaging probes which are required for PET and MRT
                      measurements,respectively. The GdDOTA complex was chosen as
                      MRI-reporting moiety due to its highthermodynamic stability
                      and kinetic inertness which are very important properties
                      for the in vivoapplication of Gd-loaded NPs with an enhanced
                      time of circulation in the body.The very challenging
                      synthesis of a DOTA-like chelator with a thiol anchoring
                      group for the directcovalent immobilization on the gold
                      surface was carried out using the “bisaminal route”.
                      Startingfrom triethylenetetramine, a $DOTA_OH-tBu4$ ester
                      was obtained, according to some optimization of adescribed
                      procedure1. The O-alkylation of $DOTA_OH-tBu4$ ester with
                      thiol-bearing electrophiles,which was followed by
                      deprotection, led to the DOTA derivatives L1 and L2 with the
                      thiol handlebeing directly attached to the macrocyclic
                      backbone. The thiol-containing NOTA L3 for radiolabelingof
                      Au-NPs with the PET radionuclide 68Ga was directly obtained
                      from a commercially available NODAGA-NHS ester through
                      reaction with cysteamine.Citrate-stabilized Au-NPs with d
                      ≈ 13 nm were prepared by citrate reduction of HAuCl4 and
                      thenfunctionalized with thiol-ending chelators by a ligand
                      place exchange reaction. The DOTAfunctionalizedAu-NPs formed
                      the corresponding complexes Au@GdL1 and Au@GdL2 with Gd
                      ionswhich were tested for their potential as contrast
                      agents. As expected, the paramagnetic Au-NPsshowed an
                      increased relaxivity (36-39 mM-1s-1, 25°C, 20 MHz) compared
                      with their small molecularanalogues GdL1/Gd2L22 (4-12
                      mM-1s-1, 25°C, 20 MHz). After that the mixture of DOTA and
                      NOTAchelating agents were grafted to the gold surface. The
                      difference in cavity size of NOTA and DOTAshould lead to a
                      selective complex formation of Au@DOTA-NOTA first with
                      paramagnetic Gd andthen with radioactive 68Ga,2 forming
                      thereby a bimodal PET-MR imaging agent.},
      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 / INM-4},
      cid          = {I:(DE-Juel1)INM-5-20090406 / I:(DE-Juel1)INM-4-20090406},
      pnm          = {573 - Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)24},
      url          = {https://juser.fz-juelich.de/record/824536},
}