title: Comparative Evaluation of the Biodistribution Profiles of a Series of Nonpeptidic Neurotensin Receptor-1 Antagonists Reveals a Promising Candidate for Theranostic Applications.
abstract: Neurotensin receptor-1 (NTR1) is a promising target for diagnostic imaging and targeted radionuclide therapy. The aim of this study was to evaluate the biodistribution profiles of a series of newly developed diarylpyrazole-based NTR1 antagonists regarding their suitability as diagnostic and potentially radiotherapeutic agents.
  
  
  METHODS
  3BP-227, 3BP-228, and 3BP-483 were labeled with (111)In and injected intravenously into NTR1-positive HT29 xenograft-bearing nude mice. At 3, 6, 12, and 24 h after administration, SPECT/CT images were acquired or mice were sacrificed for ex vivo determination of tissue-associated radioactivity.
  
  
  RESULTS
  High-contrast tumor visualization in SPECT/CT images was achieved using the 3 compounds of this study. Ex vivo biodistribution studies confirmed a high and persistent tumor uptake, peaking at 6 h after injection for (111)In-3BP-227 (8.4 ± 3.1 percentage injected dose per gram [%ID/g]) and at 3 h after injection for (111)In-3BP-228 (10.2 ± 5.3 %ID/g) and (111)In-3BP-483 (1.9 ± 0.8 %ID/g). Tumor-to-normal-tissue ratios obtained with (111)In-3BP-227 and (111)In-3BP-228 were consistently greater than 1.
  
  
  CONCLUSIONS
  On the basis of the superior biodistribution profile compared with previously reported radiolabeled NTR1 ligands, (111)In-3BP-227 is an ideal candidate for further development as a theranostic tracer.
authors.affiliation: Klinik für Radiologie und Nuklearmedizin, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schulz
authors.affiliation: Klinik für Radiologie und Nuklearmedizin, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Rohracker
authors.affiliation: Klinik für Radiologie und Nuklearmedizin, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany.
authors.forename: Marvin
authors.initials: M
authors.lastname: Stiebler
authors.affiliation: Leibniz-Institut für Neurobiologie, Magdeburg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Goldschmidt
authors.affiliation: Klinik für Radiologie und Nuklearmedizin, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany.
authors.forename: Oliver S
authors.initials: OS
authors.lastname: Grosser
authors.affiliation: 3B Pharmaceuticals GmbH, Berlin, Germany; and.
authors.forename: Frank
authors.initials: F
authors.lastname: Osterkamp
authors.affiliation: Klinik für Radiologie und Nuklearmedizin, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Pethe
authors.affiliation: 3B Pharmaceuticals GmbH, Berlin, Germany; and.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Reineke
authors.affiliation: 3B Pharmaceuticals GmbH, Berlin, Germany; and.
authors.forename: Christiane
authors.initials: C
authors.lastname: Smerling
authors.affiliation: Klinik für Radiologie und Nuklearmedizin, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany Department of Nuclear Medicine, Charité-Universitätsmedizin, Berlin, Germany holger.amthauer@med.ovgu.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Amthauer
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007205:Indium Radioisotopes; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism; D011720:Pyrazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors*; D000068936:Theranostic Nanomedicine / Q000379:methods*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007205:Indium Radioisotopes; D011720:Pyrazoles; D018028:Receptors, Neurotensin
keywords: NTR1-radiotracer; SPECT/CT; biodistribution; oncology; xenograft