Evaluation of the sonosensitizing activities of 5-aminolevulinic acid and Sn(IV) chlorin e6 in tumor-bearing chick embryos

Yoshihiro Uto; Dai Tamatani; Yusuke Mizuki; Yoshio Endo; Ikuo Nakanishi; Kei Ohkubo; Shunichi Fukuzumi; Masahiro Ishizuka; Tohru Tanaka; Daisuke Kuchiike; Kentaro Kubo; Toshio Inui; Hitoshi Hori

Evaluation of the sonosensitizing activities of 5-aminolevulinic acid and Sn(IV) chlorin e6 in tumor-bearing chick embryos

Anticancer Res. 2014 Aug;34(8):4583-7.

Authors

Affiliations

¹ Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima, Tokushima, Japan uto@bio.tokushima-u.ac.jp.
² Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima, Tokushima, Japan.
³ Central Research Resource Branch, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
⁴ Research Center for Charged Particle Therapy, National Institute of Radiological Sciences (NIRS), Chiba, Japan.
⁵ Department of Material and Life Science, Graduate School of Engineering, Osaka University, ALCA, Japan Science and Technology Agency (JST), Osaka, Japan.
⁶ SBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
⁷ Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima, Tokushima, Japan Saisei Mirai Cell Processing Center, Osaka, Japan.
⁸ Saisei Mirai Cell Processing Center, Osaka, Japan.
⁹ Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima, Tokushima, Japan Saisei Mirai Cell Processing Center, Osaka, Japan Kobe Saisei Mirai Clinic, Kobe, Japan Inui Immunotherapy Clinic, Osaka, Japan.

PMID: 25075103

Abstract

Background: Recently, 5-aminolevulinic acid (5-ALA), precursors of protoporphyrin IX (PpIX), and Sn(IV) chlorin e6 (SnCe6) have been proposed as possible sonosensitizers for sonodynamic therapy of cancer. Therefore, we evaluated the pharmacokinetic properties and sonosensitizing activities of 5-ALA and SnCe6 in vivo by using the EMT6/KU tumor-bearing chick embryos.

Results: The concentration of PpIX in tumor and liver tissues and serum increased in a time-dependent manner after the i.v. administration of 5-ALA; PpIX concentrations reached their peak level after 5-7 h. The concentration of SnCe6 reached its maximum value in the tumor tissue and serum immediately after i.v. administration. The combined treatment of 5-ALA or SnCe6 with ultrasound irradiation showed a significant antitumor effect towards EMT6/KU solid tumors.

Conclusion: We evaluated the pharmacokinetic properties and sonosensitizing activities of 5-ALA and SnCe6 in a chick embryo model and found that 5-ALA might be more suitable as a sonosensitizer than SnCe6.

Keywords: 5-aminolevulinic acid; Pharmacokinetics; Sn(IV) chlorin e6; sonosensitizer; tumor-bearing chick embryo.

MeSH terms

Aminolevulinic Acid / pharmacokinetics
Aminolevulinic Acid / pharmacology*
Animals
Cell Line, Tumor
Chick Embryo
Metalloporphyrins / pharmacokinetics
Metalloporphyrins / pharmacology*
Mice
Neoplasms, Experimental / therapy*
Protoporphyrins / metabolism
Ultrasonic Therapy*

Substances

Metalloporphyrins
Protoporphyrins
tin(IV) chlorin e6
Aminolevulinic Acid
protoporphyrin IX