TY - JOUR
T1 - 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
AU - Vangestel, Christel
AU - Van de Wiele, Christophe
AU - Mees, Gilles
AU - Mertens, Koen
AU - Staelens, Steven
AU - Reutelingsperger, Chris
AU - Pauwels, Patrick
AU - Van Damme, Nancy
AU - Peeters, Marc
PY - 2012
Y1 - 2012
N2 - As apoptosis occurs over an interval of time after administration of apoptosis-inducing therapy in tumors, the changes in technetium 99m (Tc-99m)-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). (99)mTc-(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 (99)mTc-(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 (99)mTc-(CO)(3) HisannA5 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.
AB - As apoptosis occurs over an interval of time after administration of apoptosis-inducing therapy in tumors, the changes in technetium 99m (Tc-99m)-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). (99)mTc-(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 (99)mTc-(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 (99)mTc-(CO)(3) HisannA5 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.
U2 - 10.2310/7290.2011.00034
DO - 10.2310/7290.2011.00034
M3 - Article
SN - 1535-3508
VL - 11
SP - 135
EP - 147
JO - Molecular Imaging
JF - Molecular Imaging
IS - 2
ER -