title: Development and evaluation of a novel (99m)tc-labeled annexin A5 for early detection of response to chemotherapy.
abstract: (99m)Tc-HYNIC-annexin A5 can be considered as a benchmark in the field of apoptosis imaging. However, (99m)Tc-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 (99m)Tc-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. (99m)Tc labeling was performed by a ligand exchange reaction with (99m)Tc-glucoheptonate. Biodistribution experiments for both (99m)Tc-C3(BHam)2-annexin A5 and (99m)Tc-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 (99m)Tc-C3(BHam)2-annexin A5 just after the first treatment of 5-FU was evaluated. (99m)Tc-C3(BHam)2-annexin A5 was prepared with a radiochemical purity of over 95%. In biodistribution experiments, (99m)Tc-C3(BHam)2-annexin A5 had a much lower kidney accumulation of radioactivity than (99m)Tc-HYNIC-annexin A5. In the organs for metabolism, such as liver and kidney, radioactivity after the injection of (99m)Tc-HYNIC-annexin A5 was residual for a long time. On the other hand, radioactivity after the injection of (99m)Tc-C3(BHam)2-annexin A5 gradually decreased. In therapeutic experiments, tumor growth in the mice treated with 5-FU was significantly inhibited. Accumulation of (99m)Tc-C3(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 (99m)Tc-C3(BHam)2-annexin A5 may contribute to the efficient detection of apoptotic tumor response after chemotherapy.
authors: Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
authors: Kazuma
authors: K
authors: Ogawa
authors: Katsuichi
authors: K
authors: Ohtsuki
authors: Tomomi
authors: T
authors: Shibata
authors: Miho
authors: M
authors: Aoki
authors: Morio
authors: M
authors: Nakayama
authors: Yoji
authors: Y
authors: Kitamura
authors: Masahiro
authors: M
authors: Ono
authors: Masashi
authors: M
authors: Ueda
authors: Tomoki
authors: T
authors: Doue
authors: Masahisa
authors: M
authors: Onoguchi
authors: Kazuhiro
authors: K
authors: Shiba
authors: Akira
authors: A
authors: Odani
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000138:chemical synthesis / Q000737:chemistry; D001345:Autoradiography; D001681:Biological Assay; D049109:Cell Proliferation; D020287:In Situ Nick-End Labeling; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D017304:Annexin A5; D015609:Organotechnetium Compounds; C117287:technetium Tc 99m HYNIC annexin V