@misc{oai:repo.qst.go.jp:00070877, author = {Kokuryo, Daisuke and Kano, Mitsunobu and Saga, Tsuneo and Kataoka, Kazunori and Aoki, Ichio and et.al and 國領 大介 and 狩野 光伸 and 佐賀 恒夫 and 青木 伊知男}, month = {Sep}, note = {Introduction: Size-tunable unilamellar polyion complex vesicles (PICsome) has been developed as anovel nano-vesicle for therapeutics and diagnosis (Anraku Y, et al; J Am Chem Soc., 2010). Theaccumulation of Cy5-labeled PICsomes in tumor has recently been demonstrated using a fluorescenceimaging technique (Anraku Y, et al: Chem Comm., 2011). It was found that the half-life of thePICsomes in the bloodstream can be extended over 24 hours by adjusting the size of PICsomes,providing ample time for the vesicles to accumulate in the target tissue. For the present study, PICsomes containing super paramagnetic iron oxide nanoparticle (SPIO, ferucarbotran) were developedand in vivo accumulation in mouse tumor was evaluated with MR imaging. Methods: Female Balb/c nude mice were used for in vivo MR imaging experiments. A subcutaneous tumor model was created by injecting Colon26 cancer cells (1.0 106 cells / 50 ) into the rump of the animals and allowing them to grow for 7 to 8 days. SPIO (Resovist®), which contains ferucarbotran as a major component, wasencapsulated in the Cy5-labeled PICsomes. The diameter of the PICsomes was about 100 nm. ThePICsomes were administered to the model mice via the tail vein in a 0.45 mg/kg dose of iron. As a control group, SPIO alone was injected via the tail vein of tumor model mice. All MR image acquisitionswere performed on a 7.0 Tesla animal MRI (Magnet: Kobelco and JASTEC, Japan, Console: Bruker- Biospin, Germany) with a 35 mm inner-diameter transmit/receive volume coil (Rapid Biomedical, Germany). T1-weighted and T2-weighted MR images were acquired before, immediately after, at 3, 6and 24 hours after the drug administration. Imaging parameters were as follows: TR/TE/NEX = 400 ms / 9.57 ms / 4 (T1-weighted image), 3000 ms / 30 ms / 1 (T2-weighted image); FOV = 38.4 mm 19.2 mm; and Matrix = 256 128. After MR image acquisition was completed for the PICsome group,fluorescence images were acquired using a fluorescence imager (Maestro Ex, Caliper LifeScience, USA)to confirm the accumulation of PICsomes at the tumor region. Results & Discussion: For 3-24 hours after PICsome administration, the T2-weighted signal intensity in the tumor region significantlydecreased from the intensity before administration. After 24 hours the area in tumor showing decreased T2-weighted signal expanded, and it was also possible to detect decreased signal intensity in the T1-weighted images. At the same time, the fluorescence signal also increased in the tumor region in comparison to the signal before administration. On the other hand, there were no signal changes in thesubcutaneous tumor using SPIO alone, probably because the drug was predominantly captured by the Kupffer cells in the liver (Kato N, et al: Invest Radiol., 1999). These results indicate that the SPIOcontaining PICsome passively accumulated due to EPR (Enhanced Permeability and Retention) effectand altered the MR signal in the tumor region specifically., 2012 World Molecular Imaging Congress}, title = {SPIO-containing unilamellar polyion complex vesicles (PICsome) for in vivo tumor detection using MRI}, year = {2012} }