title: Single-photon emission computed tomographic imaging of the early time course of therapy-induced cell death using technetium 99m tricarbonyl His-annexin A5 in a colorectal cancer xenograft model.
abstract: As apoptosis occurs over an interval of time after administration of apoptosis-inducing therapy in tumors, the changes in technetium 99m ((99m)Tc)-tricarbonyl (CO)₃ His-annexin A5 (His-ann A5) accumulation over time were examined. Colo205-bearing mice were divided into six treatment groups: (1) control, (2) 5-fluorouracil (5-FU; 250 mg/kg), (3) irinotecan (100 mg/kg), (4) oxaliplatin (30 mg/kg), (5) bevacizumab (5 mg/kg), and (6) panitumumab (6 mg/kg). (99m)Tc-(CO)₃ His-ann A5 was injected 4, 8, 12, 24, and 48 hours posttreatment, and micro-single-photon emission computed tomography was performed. Immunostaining of caspase-3 (apoptosis), survivin (antiapoptosis), and LC3-II (autophagy marker) was also performed. Different dynamics of (99m)Tc-(CO)₃ His-ann A5 uptake were observed in this colorectal cancer xenograft model, in response to a single dose of three different chemotherapeutics (5-FU, irinotecan, and oxaliplatin). Bevacizumab-treated mice showed no increased uptake of the radiotracer, and a peak of (99m)Tc-(CO)₃ His-ann A5 uptake in panitumumab-treated mice was observed 24 hours posttreatment, as confirmed by caspase-3 immunostaining. For irinotecan-, oxaliplatin-, and bevacizumab-treated tumors, a significant correlation was established between the radiotracer uptake and caspase-3 immunostaining (r  =  .8, p < .05; r  =  .9, p < .001; r  =  .9, p < .001, respectively). For 5-FU- and panitumumab-treated mice, the correlation coefficients were r  =  .7 (p  =  .18) and r  =  .7 (p  =  .19), respectively. Optimal timing of annexin A5 imaging after the start of different treatments in the Colo205 model was determined.
authors.affiliation: Department of Gastroenterology, Ghent University Hospital, De Pintelaan 185, 9000-B Ghent, Belgium. christel.vangestel@uza.be
authors.forename: Christel
authors.initials: C
authors.lastname: Vangestel
authors.forename: Christophe
authors.initials: C
authors.lastname: Van de Wiele
authors.forename: Gilles
authors.initials: G
authors.lastname: Mees
authors.forename: Koen
authors.initials: K
authors.lastname: Mertens
authors.forename: Steven
authors.initials: S
authors.lastname: Staelens
authors.forename: Chris
authors.initials: C
authors.lastname: Reutelingsperger
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.forename: Nancy
authors.initials: N
authors.lastname: Van Damme
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
mesh_terms: D000818:Animals; D017304:Annexin A5; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015609:Organotechnetium Compounds; D012097:Repressor Proteins / Q000378:metabolism; D000077022:Survivin; D013667:Technetium; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D017304:Annexin A5; D000970:Antineoplastic Agents; C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D015609:Organotechnetium Compounds; D012097:Repressor Proteins; D000077022:Survivin; C575424:technetium 99m tricarbonyl His-annexin A5; D013667:Technetium; D053148:Caspase 3