title: 99mTc-Duramycin SPECT Imaging of Early Tumor Response to Targeted Therapy: A Comparison with18F-FDG PET.
abstract: Molecular imaging of cell death may provide a detailed readout of the cellular response to novel therapies and prognostic information on tumor treatment efficacy, assisting in the design of individualized therapy. We compared the predictive power of cell death imaging using99mTc-duramycin with the current gold standard18F-FDG for treatment response evaluation after targeted therapy.Methods:Early therapy response evaluation was assessed by99mTc-duramycin SPECT and18F-FDG PET imaging in treatment-sensitive COLO205 and treatment-resistant HT29 human colorectal cancer xenografts 24 h after a single dose of conatumumab or IgG1 control. The specificity of99mTc-duramycin for apoptosis was assessed using99mTc-linear duramycin control radiotracer. Radiotracer uptake was validated ex vivo by γ-counting and autoradiography and compared with cleaved caspase-3 (CC3) activation and DNA fragmentation (TdT-mediated dUTP nick-end labeling [TUNEL]). Data were analyzed with the Studentttest and Pearson correlation. All statistical tests were 2-sided.Results:COLO205 tumor uptake of99mTc-duramycin was increased 7-fold from baseline in conatumumab- versus IgG1-treated control mice (P< 0.001), in good correlation with histologic analysis of apoptosis (CC3,r= 0.842, and TUNEL,r= 0.894;P< 0.001). No response was detected in HT29 tumors. No change in99mTc-linear duramycin uptake could be detected in COLO205 tumors after treatment, indicating specificity of the99mTc-duramycin tumor signal.18F-FDG uptake was not significantly increased from baseline in conatumumab- versus IgG1-treated COLO205 and HT29 tumor-bearing mice (P= 0.104 and 0.779, respectively) and did not correlate with immunohistochemical evidence of apoptosis.Conclusion:We have demonstrated that99mTc-duramycin specifically accumulates in apoptotic tumors in which18F-FDG was not able to differentiate responding from nonresponding tumors early after treatment.99mTc-duramycin holds promise as a noninvasive imaging radiotracer for early treatment evaluation in the clinic.
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Wilrijk, Belgium leonie.wyffels@uza.be filipe.elvas@uantwerpen.be.|Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Filipe
authors.initials: F
authors.lastname: Elvas
authors.affiliation: Laboratory of Molecular Pathology, Cell Biology and Histology, University of Antwerp, Wilrijk, Belgium; and.
authors.forename: Jan
authors.initials: J
authors.lastname: Boddaert
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Wilrijk, Belgium.|Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Christel
authors.initials: C
authors.lastname: Vangestel
authors.affiliation: Molecular Targeting Technologies, Inc., West Chester, Pennsylvania.
authors.forename: Koon
authors.initials: K
authors.lastname: Pak
authors.affiliation: Molecular Targeting Technologies, Inc., West Chester, Pennsylvania.
authors.forename: Brian
authors.initials: B
authors.lastname: Gray
authors.affiliation: Laboratory of Molecular Pathology, Cell Biology and Histology, University of Antwerp, Wilrijk, Belgium; and.
authors.forename: Samir
authors.initials: S
authors.lastname: Kumar-Singh
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Wilrijk, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Staelens
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Wilrijk, Belgium.|Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stroobants
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Wilrijk, Belgium leonie.wyffels@uza.be filipe.elvas@uantwerpen.be.|Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Leonie
authors.initials: L
authors.lastname: Wyffels
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D017209:Apoptosis; D001430:Bacteriocins / Q000378:metabolism / Q000493:pharmacokinetics; D001692:Biological Transport; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019788:Fluorodeoxyglucose F18; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D015609:Organotechnetium Compounds / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D013997:Time Factors; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D001430:Bacteriocins; D015609:Organotechnetium Compounds; C578182:technetium 99m HYNIC-duramycin; D019788:Fluorodeoxyglucose F18; C554537:conatumumab
keywords: 99mTc-duramycin SPECT; cell death imaging; colorectal cancer; response evaluation; targeted therapy