Tumor Targeting of Radiolabeled PEGylated-liposome in mice CT-26 Animal Model

• Main Authors: Yi-Ching Lu, 呂怡青
• Other Authors: Hsin-Ell Wang
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/73994276806802669120

碩士 === 國立陽明大學 === 放射醫學科學研究所 === 94 === The in vitro evaluation, biodistribution and pharmacokinetics of 111In-labelled DTPA- and VNB-liposomes in tumor-bearing BALB/c mice were studied to examine their possible role of 111In-labelled liposomes as tumor targeting agents. Methods: The DTPA/VNB-liposome was synthesized with a medium size of 110 nm, conjugated with 111In-(oxine)3 or 111In-ionomycin conjugator to afford 111In-liposomes. The stability of 111In-liposomes in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of 111In-liposomes after i.v. injection into CT-26 tumor-bearing BALB/c mice were studied. Radiation toxicity of 111In-liposomes after i.v. injection into BALB/c mice was also investigated. Results: The incorporation efficiency of 111In into liposomes was 95% in both methods. After incubation at 37℃ for 72 h in serum, more than 70% of radioactivity was still retained in the intact 111In-DTPA- and 111In-VNB-liposomes labeled by oxine. However, there was only 53.5% and 40.9% of radioactivity was still retained in 111In-DTPA- and 111In-VNB- liposomes labeled by ionomycin after incubation at 37℃ for 5 mins in serum. It decreased to 25.3% and 18.6% after incubation at 37℃ for 72 h in serum, respectively. The biodistribution of 111In-DTPA-liposome showed that the radioactivity in the blood decreased from 23.14 ± 8.16 %ID/g at 1 h to 0.02 ± 0.00 %ID/g at 72 h post injection (p.i.). Accumulation of radioactivity in tumors reached a maximum at 48 h p.i. The half-life of 111In-DTPA- and 111In-VNB- liposomes in blood was 10.2 h and 7.1h, respectively. Scintigraphic imaging with 111In-DTPA-liposomes showed unambiguous tumor images at 48 h p.i. Radiation toxicity investigation showed that no critical toxicity was observed in mice injected 111In-DTPA-liposomes. IV Conclusions: This study demonstrates prolonged retention of radiolabeled lightly-pegylated liposomes within the tumor after i.v. injection and confirms the capability of 111In-liposomes to target CT-26 tumors in mice.