title: Characterization of [(99m)Tc]Duramycin as a SPECT Imaging Agent for Early Assessment of Tumor Apoptosis.
abstract: OBJECTIVE
  We investigated the usefulness of [(99m)Tc]duramycin for monitoring early response to cancer therapy in mice, with an eye towards clinical translation.
  
  
  METHODS
  [(99m)Tc]Duramycin was injected in healthy CD1-/- mice to estimate human [(99m)Tc]duramycin radiation dose. [(99m)Tc]Duramycin single-photon emission computed tomography (SPECT) imaging of apoptosis was evaluated in a mouse model of colorectal cancer treated with irinotecan and validated ex vivo using autoradiography, cleaved caspase-3, and TdT-mediated dUTP nick-end labeling (TUNEL) histology of the tumors.
  
  
  RESULTS
  The mean effective dose was estimated to be 3.74 × 10(-3) ± 3.43 × 10(-4) mSv/MBq for non-purified and 3.19 × 10(-3) ± 2.16 × 10(-4) mSv/MBq for purified [(99m)Tc]duramycin. [(99m)Tc]Duramycin uptake in vivo following therapy increased significantly in apoptotic irinotecan-treated tumors (p = 0.008). Radioactivity in the tumors positively correlated with cleaved caspase-3 (r = 0.85, p < 0.001) and TUNEL (r = 0.92, p < 0.001) staining.
  
  
  CONCLUSIONS
  [(99m)Tc]Duramycin can be used to detect early chemotherapy-induced tumor cell death, and thus, may be a prospective candidate for clinical SPECT imaging of tumor response to therapy.
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.|Department of Nuclear Medicine, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium.
authors.forename: Filipe
authors.initials: F
authors.lastname: Elvas
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.|Department of Nuclear Medicine, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium.
authors.forename: Christel
authors.initials: C
authors.lastname: Vangestel
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: Rapic
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Verhaeghe
authors.affiliation: Molecular Targeting Technologies, Inc., West Chester, PA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Gray
authors.affiliation: Molecular Targeting Technologies, Inc., West Chester, PA, USA.
authors.forename: Koon
authors.initials: K
authors.lastname: Pak
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.|Department of Nuclear Medicine, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stroobants
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Staelens
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium. leonie.wyffels@uza.be.|Department of Nuclear Medicine, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium. leonie.wyffels@uza.be.
authors.forename: Leonie
authors.initials: L
authors.lastname: Wyffels
mesh_terms: D000818:Animals; D017209:Apoptosis; D001430:Bacteriocins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D013667:Technetium / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D001430:Bacteriocins; D010455:Peptides; C040522:duramycin; D013667:Technetium
keywords: 99mTc; Apoptosis; Chemotherapy; Duramycin; Preclinical dosimetry; Small-animal SPECT imaging