摘要
AIM: To investigate the biological effects of internal irradiation, and the therapeutic effectiveness was assessed of ^(131)I-labeled anti-epidermal growth factor receptor(EGFR) liposomes, derived from cetuximab, when used as a tumor-targeting carrier in a colorectal cancer mouse model.METHODS: We described the liposomes and characterized their EGFR-targeted binding and cellular uptake in EGFR-overexpressing LS180 colorectal cancer cells. After intra-tumor injections of 74 MBq(740 MBq/m L) ^(131)I-anti EGFR-BSA-PCL, we investigated the biological effects of internal irradiation and the therapeutic efficacy of ^(131)I-anti EGFR-BSA-PCL on colorectal cancer in a male BALB/c mouse model. Tumor size, body weight, histopathology, and SPECT imaging were monitored for 33 d post-therapy.RESULTS: The rapid radioiodine uptake of ^(131)I-antiEGFR-BSA-PCL and ^(131)I-BSA-PCL reached maximum levels at 4 h after incubation, and the ^(131)I uptake of ^(131)I-anti EGFR-BSA-PCL was higher than that of ^(131)I-BSAPCL in vitro. The ^(131)I tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor. Furthermore, a tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor and reached its maximal uptake value of 21.0 ± 1.01 %ID/g(%ID/g is the percentage injected dose per gram of tissue) at 72 h following therapy; the drug concentration in the tumor was higher than that in the liver, heart, colon, or spleen. Tumor size measurements showed that tumor development was significantly inhibited by treatments with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL. The volume of tumor increased, and treatment rate with ^(131)I-anti EGFR-BSA-PCL was 124% ± 7%, lower than that with ^(131)I-BSA-PCL(127% ± 9%), ^(131)I(143% ± 7%), and normal saline(146% ± 10%). The percentage losses in original body weights were 39% ± 3%, 41% ± 4%, 49% ± 5%, and 55% ± 13%, respectively. The best survival and cure rates were obtained in the group treated with ^(131)I-anti EGFR-BSA-PCL. The animals injected with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL showed more uniform focused liposome distribution within the tumor area.CONCLUSION: This study demonstrated the potential beneficial application of ^(131)I-anti EGFR-BSA-PCL for treating colorectal cancer. ^(131)I-anti EGFR-BSA-PCL suppressed the development of xenografted colorectal cancer in nude mice, thereby providing a novel candidate for receptor-mediated targeted radiotherapy.
AIM: To investigate the biological effects of internal irradiation, and the therapeutic effectiveness was assessed of <sup>131</sup>I-labeled anti-epidermal growth factor receptor (EGFR) liposomes, derived from cetuximab, when used as a tumor-targeting carrier in a colorectal cancer mouse model.METHODS: We described the liposomes and characterized their EGFR-targeted binding and cellular uptake in EGFR-overexpressing LS180 colorectal cancer cells. After intra-tumor injections of 74 MBq (740 MBq/mL) <sup>131</sup>I-antiEGFR-BSA-PCL, we investigated the biological effects of internal irradiation and the therapeutic efficacy of <sup>131</sup>I-antiEGFR-BSA-PCL on colorectal cancer in a male BALB/c mouse model. Tumor size, body weight, histopathology, and SPECT imaging were monitored for 33 d post-therapy.RESULTS: The rapid radioiodine uptake of <sup>131</sup>I-antiEGFR-BSA-PCL and <sup>131</sup>I-BSA-PCL reached maximum levels at 4 h after incubation, and the <sup>131</sup>I uptake of <sup>131</sup>I-antiEGFR-BSA-PCL was higher than that of <sup>131</sup>I-BSA-PCL in vitro. The <sup>131</sup>I tissue distribution assay revealed that <sup>131</sup>I-antiEGFR-BSA-PCL was markedly taken up by the tumor. Furthermore, a tissue distribution assay revealed that <sup>131</sup>I-antiEGFR-BSA-PCL was markedly taken up by the tumor and reached its maximal uptake value of 21.0 ± 1.01 %ID/g (%ID/g is the percentage injected dose per gram of tissue) at 72 h following therapy; the drug concentration in the tumor was higher than that in the liver, heart, colon, or spleen. Tumor size measurements showed that tumor development was significantly inhibited by treatments with <sup>131</sup>I-antiEGFR-BSA-PCL and <sup>131</sup>I-BSA-PCL. The volume of tumor increased, and treatment rate with <sup>131</sup>I-antiEGFR-BSA-PCL was 124% ± 7%, lower than that with <sup>131</sup>I-BSA-PCL (127% ± 9%), <sup>131</sup>I (143% ± 7%), and normal saline (146% ± 10%). The percentage losses in original body weights were 39% ± 3%, 41% ± 4%, 49% ± 5%, and 55% ± 13%, respectively. The best survival and cure rates were obtained in the group treated with <sup>131</sup>I-antiEGFR-BSA-PCL. The animals injected with <sup>131</sup>I-antiEGFR-BSA-PCL and <sup>131</sup>I-BSA-PCL showed more uniform focused liposome distribution within the tumor area.CONCLUSION: This study demonstrated the potential beneficial application of <sup>131</sup>I-antiEGFR-BSA-PCL for treating colorectal cancer. <sup>131</sup>I-antiEGFR-BSA-PCL suppressed the development of xenografted colorectal cancer in nude mice, thereby providing a novel candidate for receptor-mediated targeted radiotherapy.
基金
Supported by the National Natural Science Foundation of China,No.81301244(to Li W)
the National Key Clinical Specialty Project
