Development and evaluation of a novel 99mTc-labeled annexin A5 for early detection of response to chemotherapy

Kazuma Ogawa, Katsuichi Ohtsuki, Tomomi Shibata, Miho Aoki, Morio Nakayama, Yoji Kitamura, Masahiro Ono, Masashi Ueda, Tomoki Doue, Masahisa Onoguchi, Kazuhiro Shiba, Akira Odani

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere81191
JournalPLoS One
Volume8
Issue number12
DOIs
Publication statusPublished - Dec 4 2013

Fingerprint

Chemotherapy
Annexin A5
drug therapy
Tumors
Drug Therapy
neoplasms
Radioactivity
Fluorouracil
kidneys
Neoplasms
mice
apoptosis
image analysis
Liver
injection
Kidney
therapeutics
liver
Bearings (structural)
Apoptosis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ogawa, K., Ohtsuki, K., Shibata, T., Aoki, M., Nakayama, M., Kitamura, Y., ... Odani, A. (2013). Development and evaluation of a novel 99mTc-labeled annexin A5 for early detection of response to chemotherapy. PLoS One, 8(12), [e81191]. https://doi.org/10.1371/journal.pone.0081191

Development and evaluation of a novel 99mTc-labeled annexin A5 for early detection of response to chemotherapy. / Ogawa, Kazuma; Ohtsuki, Katsuichi; Shibata, Tomomi; Aoki, Miho; Nakayama, Morio; Kitamura, Yoji; Ono, Masahiro; Ueda, Masashi; Doue, Tomoki; Onoguchi, Masahisa; Shiba, Kazuhiro; Odani, Akira.

In: PLoS One, Vol. 8, No. 12, e81191, 04.12.2013.

Research output: Contribution to journalArticle

Ogawa, K, Ohtsuki, K, Shibata, T, Aoki, M, Nakayama, M, Kitamura, Y, Ono, M, Ueda, M, Doue, T, Onoguchi, M, Shiba, K & Odani, A 2013, 'Development and evaluation of a novel 99mTc-labeled annexin A5 for early detection of response to chemotherapy', PLoS One, vol. 8, no. 12, e81191. https://doi.org/10.1371/journal.pone.0081191
Ogawa, Kazuma ; Ohtsuki, Katsuichi ; Shibata, Tomomi ; Aoki, Miho ; Nakayama, Morio ; Kitamura, Yoji ; Ono, Masahiro ; Ueda, Masashi ; Doue, Tomoki ; Onoguchi, Masahisa ; Shiba, Kazuhiro ; Odani, Akira. / Development and evaluation of a novel 99mTc-labeled annexin A5 for early detection of response to chemotherapy. In: PLoS One. 2013 ; Vol. 8, No. 12.
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