@misc{oai:repo.qst.go.jp:00069466,
 author = {Aoki, Ichio and Yoneyama, Misao and Minemoto, Yuzuru and Koyama, Takayoshi and Kershaw, Jeffrey and Ishizaka, Yukihito and Kanno, Iwao and et.al and 青木 伊知男 and 米山 操 and 峯本 譲 and 小山 貴芳 and Ｋｅｒｓｈａｗ Ｊｅｆｆｒｅｙ and 石坂 幸人 and 菅野 巖},
 month = {Sep},
 note = {Presentation Number 1569
\nDevelopment of Multimodal Thermosensitive Polymer-Modified Liposome (MTPL) as a Carrier for MRI and Optical Imaging
\nIchio Aoki1, Misao Yoneyama1, Jun Hirose2, Yuzuru Minemoto3, Takayoshi Koyama3, Sadahito Aoshima4, Jeff Kershaw1, Kenji Kono2, Yukihito Ishizaka3, Iwao Kanno1, 1National Institute of Radiological Sciences, Japan; 2Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Japan; 3Department of Intractable Diseases, International Medical Center of Japan, Japan; 4Department of Polymer Science, Graduate School of Sciences, Osaka University, Japan. Contact e-mail: aoki@nirs.go.jp
\nIntroduction: A liposomal drug-delivery system (DDS) will be help to avoid the side effects of chemotherapy by releasing anticancer drug at the tumor site. To improve the liposomal DDS, we developed a multimodal thermo-sensitive polymer-modified liposomes (MTPL) and added new factors, long-term stability of the liposome in-vivo and multimodal observation with both MRI and optical imaging. The purpose of this study was to investigate whether 1) MRI and optical imaging can visualize accumulation of MTPL in the tumor, 2) MTPL allows visualization of the drug release after being triggered by mild-heating 8h after administration, and 3) MTPL can provide sufficient anti-tumor effects.
Methods: EYPC, DOPE, Chol, PEG(2000)-PE, EOEOVE-ODVE and Rho-PE (23.4/54.6/15/4/2/1, mol%) (53.3 mg) were dissolved in a mixture of chloroform and methanol. The obtained thin lipid/copolymer-mixed membrane was further dried under vacuum for 4h and dispersed in an aqueous MnSO4 (300 mM). Female Bulb/c nude mice (n=13, 17.5 plus-minus 2.5 g) were used. Colon 26 cancer cells were transplanted subcutaneously in the femurs of the mice. In-vivo optical imaging was performed 0, 4 and 8-h after the MTPL administration. T1-weighted MR images were acquired prior to heating using a 7.0T MRI 8 hours after the administration. Thereafter, one side of the tumor site was heated at 42.5 Centigrade for 10 minutes. MRI acquisition was performed again after heating. Mice were kept and observed in normal cages for 14 days.
Results and Discussion: MTPLs that contain doxorubicin for chemotherapy, MnSO4 as an MRI agent, and the fluorescent dye Rhodamine for in-vivo optical imaging were synthesized. MRI signal intensity was enhanced after mild-heating 8h after the administration. The anti-tumor effect was clear for 14 days after the treatment. This method provides a system consisting of diagnostic, treatment, and evaluation.
Disclosure of author financial interest or relationships:
\nI. Aoki, None; M. Yoneyama, None; J. Hirose, None; Y. Minemoto, None; T. Koyama, None; S. Aoshima, None; J. Kershaw, None; K. Kono, None; Y. Ishizaka, None; I. Kanno, None., 2008 World Molecular Imaging Congress},
 title = {Development of Multimodal Thermosensitive Polymer-Modified Liposome (MTPL) as a Carrier for MRI and Optical Imaging},
 year = {2008}
}