14 research outputs found
Development and evaluation of a novel 99mTc-labeled annexin A5 for early detection of response to chemotherapy
金沢大学疾患モデル総合研究センター99mTc-HYNIC-annexin A5 can be considered as a benchmark in the field of apoptosis imaging. However, 99mTc-HYNIC-annexin A5 has characteristics of high uptake and long retention in non-target tissues such as kidney and liver. To minimize this problem, we developed a novel 99mTc-labeled annexin A5 using a bis(hydroxamamide) derivative [C3(BHam)2] as a bifunctional chelating agent, and evaluated its usefulness as an imaging agent for detecting apoptosis. The amino group of C3(BHam)2 was converted to a maleimide group, and was coupled to thiol groups of annexin A5 pretreated with 2-iminothiolane. 99mTc labeling was performed by a ligand exchange reaction with 99mTc-glucoheptonate. Biodistribution experiments for both 99mTc-C3(BHam)2-annexin A5 and 99mTc-HYNIC-annexin A5 were performed in normal mice. In addition, in tumor-bearing mice, the relationship between the therapeutic effects of chemotherapy (5-FU) and the tumor accumulation of 99mTc-C 3(BHam)2-annexin A5 just after the first treatment of 5-FU was evaluated. 99mTc-C3(BHam)2-annexin A5 was prepared with a radiochemical purity of over 95%. In biodistribution experiments, 99mTc-C3(BHam)2-annexin A5 had a much lower kidney accumulation of radioactivity than 99mTc-HYNIC- annexin A5. In the organs for metabolism, such as liver and kidney, radioactivity after the injection of 99mTc-HYNIC-annexin A5 was residual for a long time. On the other hand, radioactivity after the injection of 99mTc-C3(BHam)2-annexin A5 gradually decreased. In therapeutic experiments, tumor growth in the mice treated with 5-FU was significantly inhibited. Accumulation of 99mTc-C 3(BHam)2-annexin A5 in tumors significantly increased after 5-FU treatment. The accumulation of radioactivity in tumor correlated positively with the counts of TUNEL-positive cells. These findings suggest that 99mTc-C3(BHam)2-annexin A5 may contribute to the efficient detection of apoptotic tumor response after chemotherapy. © 2013 Ogawa et al.CC-BY 4.
Development and Evaluation of a Novel 99mTc-Labeled Annexin A5 for Early Detection of Response to Chemotherapy
99mTc-HYNIC-annexin A5 can be considered as a benchmark in the field of apoptosis imaging. However, 99mTc-HYNIC-annexin A5 has characteristics of high uptake and long retention in non-target tissues such as kidney and liver. To minimize this problem, we developed a novel 99mTc-labeled annexin A5 using a bis(hydroxamamide) derivative [C3(BHam)2] as a bifunctional chelating agent, and evaluated its usefulness as an imaging agent for detecting apoptosis. The amino group of C3(BHam)2 was converted to a maleimide group, and was coupled to thiol groups of annexin A5 pretreated with 2-iminothiolane. 99mTc labeling was performed by a ligand exchange reaction with 99mTc-glucoheptonate. Biodistribution experiments for both 99mTc-C3(BHam)2-annexin A5 and 99mTc-HYNIC-annexin A5 were performed in normal mice. In addition, in tumor-bearing mice, the relationship between the therapeutic effects of chemotherapy (5-FU) and the tumor accumulation of 99mTc-C 3(BHam)2-annexin A5 just after the first treatment of 5-FU was evaluated. 99mTc-C3(BHam)2-annexin A5 was prepared with a radiochemical purity of over 95%. In biodistribution experiments, 99mTc-C3(BHam)2-annexin A5 had a much lower kidney accumulation of radioactivity than 99mTc-HYNIC- annexin A5. In the organs for metabolism, such as liver and kidney, radioactivity after the injection of 99mTc-HYNIC-annexin A5 was residual for a long time. On the other hand, radioactivity after the injection of 99mTc-C3(BHam)2-annexin A5 gradually decreased. In therapeutic experiments, tumor growth in the mice treated with 5-FU was significantly inhibited. Accumulation of 99mTc-C 3(BHam)2-annexin A5 in tumors significantly increased after 5-FU treatment. The accumulation of radioactivity in tumor correlated positively with the counts of TUNEL-positive cells. These findings suggest that 99mTc-C3(BHam)2-annexin A5 may contribute to the efficient detection of apoptotic tumor response after chemotherapy
Clinical characteristics and morphologic features of isolated noncompaction of the ventricular myocardium: electrocardiogram-gated magnetic resonance imaging can elucidate more accurate biventricular structures
Autoradiography.
<p>Representative autoradiographic images (A, D) and TUNEL-staining images (B, C, E, F) for adjacent tumor sections from mice treated with 5-FU (A, B, C) or non-treatment mice (D, E, F). Scale bar = 1 mm.</p
Correlation between TUNEL-positive cells and radioacitvity in tumor section.
<p>Correlation between the number of TUNEL-positive cells in each grid (0.45 mm×0.55 mm) of a tumoral section and <sup>99m</sup>Tc-C<sub>3</sub>(BHam)<sub>2</sub>-annexin A5 accumulation (%dose) determined by autoradiography in each corresponding grid of an adjacent section from mice treated with 5-FU (A) or non-treatment mice (B).</p
TUNEL-stained images.
<p>Representative TUNEL-stained images of tumor specimen in control mouse (A), 100 mg/kg of 5-FU-treated mouse (B), and 150 mg/kg of 5-FU-treated mouse (C). Scale bar = 100 µm.</p
Preparation of C<sub>3</sub>(BHam)<sub>2</sub>-annexin A5.
<p>Preparation of C<sub>3</sub>(BHam)<sub>2</sub>-annexin A5.</p
Tumor grouth curves.
<p>Curves depicting inhibition of the growth of colon-26 in treatment with 150 mg/kg of 5-FU (closed circles) or 100 mg/kg of 5-FU (closed diamonds) compared with untreated control group (open circles). Data are expressed as tumor volume relative to that on the day of treatment (mean ± SEM for 5 mice). Significance was determined using one-way ANOVA followed by Dunnett's post hoc test (**<i>p</i><0.01, *<i>p</i><0.05 vs. control group).</p
Tumore uptake.
<p>Comparison of tumor uptake of (A) <sup>99m</sup>Tc-C<sub>3</sub>(BHam)<sub>2</sub>-annexin A5 (mean ± SD for 4-6 mice) and (B) <sup>99m</sup>Tc-HYNIC-annexin A5 (mean ± SD for 6 mice) at 4 h after injection after 5-FU treatment or non-treatment. In the case of <sup>99m</sup>Tc-C<sub>3</sub>(BHam)<sub>2</sub>-annexin A5, significance was determined using one-way ANOVA followed by Dunnett's post hoc test (**<i>p</i><0.01, *<i>p</i><0.05 vs. control group). In the case of <sup>99m</sup>Tc-HYNIC-annexin A5, significance was determined using Students' t test (*<i>p</i><0.05 vs. control group).</p
Correlation between TUNEL-positive cells and tumor uptake.
<p>Correlation between the number of TUNEL-positive cells in tumor after first 5-FU therapy and <sup>99m</sup>Tc-C<sub>3</sub>(BHam)<sub>2</sub>-annexin A5 accumulation (%dose/g) (A) or <sup>99m</sup>Tc-HYNIC-annexin A5 accumulation (%dose/g) (B) in corresponding tumor tissue.</p