@article{HartrampfWeinzierlBucketal.2022,
  author    = {Hartrampf, Philipp E. and Weinzierl, Franz-Xaver and Buck, Andreas K. and Rowe, Steven P. and Higuchi, Takahiro and Seitz, Anna Katharina and K{\"u}bler, Hubert and Schirbel, Andreas and Essler, Markus and Bundschuh, Ralph A. and Werner, Rudolf A.},
  title     = {Matched-pair analysis of [\(^{177}\)Lu]Lu-PSMA I\&T and [\(^{177}\)Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {49},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {9},
  doi       = {10.1007/s00259-022-05744-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324581},
  pages     = {3269-3276},
  year      = {2022},
  abstract  = {Background Labelled with lutetium-177, the urea-based small molecules PSMA I\&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC). In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT. Materials and methods A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [\(^{177}\)Lu]Lu-PSMA I\&T, and a matched cohort of 55 patients treated with [\(^{177}\)Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared. Results Toxicity assessment revealed grade III anaemia in a single patient (1.8\%) for [\(^{177}\)Lu]Lu-PSMA I\&T and five (9.1\%) for [\(^{177}\)Lu]Lu-PSMA-617. In addition, one (1.9\%) grade III thrombopenia for [\(^{177}\)Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [\(^{177}\)Lu]Lu-PSMA I\&T did not differ significantly when compared to patients treated with [\(^{177}\)Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89). Conclusion In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed.},
  language  = {en}
}
@article{WernerSayehliHaenscheidetal.2023,
  author    = {Werner, Rudolf A. and Sayehli, Cyrus and H{\"a}nscheid, Heribert and Higuchi, Takahiro and Serfling, Sebastian E. and Fassnacht, Martin and Goebeler, Maria-Elisabeth and Buck, Andreas K. and Kroiss, Matthias},
  title     = {Successful combination of selpercatinib and radioiodine after pretherapeutic dose estimation in RET-altered thyroid carcinoma},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {50},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {6},
  doi       = {10.1007/s00259-022-06061-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324435},
  pages     = {1833-1834},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{HiguchiWerner2023,
  author    = {Higuchi, Takahiro and Werner, Rudolf A.},
  title     = {Unfolding the cardioprotective potential of sigma-1 receptor-directed molecular imaging},
  series = {Journal of Nuclear Cardiology},
  volume    = {30},
  journal   = {Journal of Nuclear Cardiology},
  number    = {2},
  doi       = {10.1007/s12350-022-03077-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324600},
  pages     = {662-664},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{TutovChenWerneretal.2023,
  author    = {Tutov, Anna and Chen, Xinyu and Werner, Rudolf A. and M{\"u}hlig, Saskia and Zimmermann, Thomas and Nose, Naoko and Koshino, Kazuhiro and Lapa, Constantin and Decker, Michael and Higuchi, Takahiro},
  title     = {Rationalizing the binding modes of PET radiotracers targeting the norepinephrine transporter},
  series = {Pharmaceutics},
  volume    = {15},
  journal   = {Pharmaceutics},
  number    = {2},
  issn      = {1999-4923},
  doi       = {10.3390/pharmaceutics15020690},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303949},
  year      = {2023},
  abstract  = {Purpose: A new PET radiotracer \(^{18}\)F-AF78 showing great potential for clinical application has been reported recently. It belongs to a new generation of phenethylguanidine-based norepinephrine transporter (NET)-targeting radiotracers. Although many efforts have been made to develop NET inhibitors as antidepressants, systemic investigations of the structure-activity relationships (SARs) of NET-targeting radiotracers have rarely been performed. Methods: Without changing the phenethylguanidine pharmacophore and 3-fluoropropyl moiety that is crucial for easy labeling, six new analogs of \(^{18}\)F-AF78 with different meta-substituents on the benzene-ring were synthesized and evaluated in a competitive cellular uptake assay and in in vivo animal experiments in rats. Computational modeling of these tracers was established to quantitatively rationalize the interaction between the radiotracers and NET. Results: Using non-radiolabeled reference compounds, a competitive cellular uptake assay showed a decrease in NET-transporting affinity from meta-fluorine to iodine (0.42 and 6.51 µM, respectively), with meta-OH being the least active (22.67 µM). Furthermore, in vivo animal studies with radioisotopes showed that heart-to-blood ratios agreed with the cellular experiments, with AF78(F) exhibiting the highest cardiac uptake. This result correlates positively with the electronegativity rather than the atomic radius of the meta-substituent. Computational modeling studies revealed a crucial influence of halogen substituents on the radiotracer-NET interaction, whereby a T-shaped π-π stacking interaction between the benzene-ring of the tracer and the amino acid residues surrounding the NET binding site made major contributions to the different affinities, in accordance with the pharmacological data. Conclusion: The SARs were characterized by in vitro and in vivo evaluation, and computational modeling quantitatively rationalized the interaction between radiotracers and the NET binding site. These findings pave the way for further evaluation in different species and underline the potential of AF78(F) for clinical application, e.g., cardiac innervation imaging or molecular imaging of neuroendocrine tumors.},
  language  = {en}
}