Chun-Yi Wu1, Jo-Hsin Tang2, Pei-Chia Chan2,3, Jia-Je Li2,3, Ming-Hsien Lin4, Chih-Chieh Shen5, Ren-Shyan Liu2,6,7, Hsin-Ell Wang8,9. 1. Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan. 2. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. 3. Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan. 4. Department of Nuclear Medicine, Taipei City Hospital Zhongxiao Branch, Taipei, Taiwan. 5. Department of Nuclear Medicine, Cheng Hsin General Hospital, Taipei, Taiwan. chihchieh0330@yahoo.com.tw. 6. Department of Nuclear Medicine and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, Taiwan. 7. Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan. 8. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan. hewang@ym.edu.tw. 9. Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan. hewang@ym.edu.tw.
Abstract
PURPOSE: Surgical resection is the standard treatment for localized colorectal cancer, which is the most common type of gastrointestinal cancer. However, over 40 % cases are diagnosed metastasized and apparently inoperable. Systemic chemotherapy provides an alternative to these patients. This study aims to evaluate the therapeutic potential of liposomal doxorubicin (lipoDox) in combination with liposomal vinorelbine (lipoVNB) in a CT-26 colon carcinoma-bearing mouse model. PROCEDURES: The in vitro cytotoxicity of Dox and VNB on CT-26 cancer cells was determined by MTT and colony formation assays. Mice were subcutaneously inoculated with 2 × 105 of CT-26 cells in the right hind flank. When tumor size reached 200 ± 50 mm3, mice were assigned to receive different treatment protocols. The pharmacokinetics, micro single-photon emission computed tomography/x-ray computed tomography imaging, biodistribution, and immunohistochemical staining studies were performed to survey the therapeutic efficacy of each regimen. RESULTS: Based on the results of pharmacokinetic study, co-administration of lipoDox and lipoVNB did not affect their individual systemic distribution, while lipoDox retained longer in blood than lipoVNB did. Superior tumor growth retardation was observed in the group received lipoDox plus lipoVNB administration (1 mg/kg each, namely D1V1) than those injected with lipoDox plus VNB (1 mg/kg each, namely D1fV1). No severe side effects were detected in each group. The tumor-to-muscle ratio (T/M) derived from 3'-dexoy-3'-[18F]fluorothymidine ([18F]FLT) micro positron emission tomography (PET) images of D1V1- and D1fV1-treated mice and the controls on day 7 was 6.88 ± 0.54, 7.50 ± 0.84, and 9.87 ± 0.73, respectively, suggesting that D1V1 is a more efficacious regimen against CT-26 xenografts. The results of proliferating cell nuclear antigen (PCNA) immunohistochemical staining were consistent with those findings obtained from [18F]FLT microPET imaging. CONCLUSION: This study demonstrated that lipoDox in combination with lipoVNB was more efficacious than clinically used regimen, lipoDox plus VNB, in the treatment of colon carcinoma and [18F]FLT-PET is a promising approach in monitoring the treatment outcome at early stage.
PURPOSE: Surgical resection is the standard treatment for localized colorectal cancer, which is the most common type of gastrointestinal cancer. However, over 40 % cases are diagnosed metastasized and apparently inoperable. Systemic chemotherapy provides an alternative to these patients. This study aims to evaluate the therapeutic potential of liposomal doxorubicin (lipoDox) in combination with liposomal vinorelbine (lipoVNB) in a CT-26 colon carcinoma-bearing mouse model. PROCEDURES: The in vitro cytotoxicity of Dox and VNB on CT-26 cancer cells was determined by MTT and colony formation assays. Mice were subcutaneously inoculated with 2 × 105 of CT-26 cells in the right hind flank. When tumor size reached 200 ± 50 mm3, mice were assigned to receive different treatment protocols. The pharmacokinetics, micro single-photon emission computed tomography/x-ray computed tomography imaging, biodistribution, and immunohistochemical staining studies were performed to survey the therapeutic efficacy of each regimen. RESULTS: Based on the results of pharmacokinetic study, co-administration of lipoDox and lipoVNB did not affect their individual systemic distribution, while lipoDox retained longer in blood than lipoVNB did. Superior tumor growth retardation was observed in the group received lipoDox plus lipoVNB administration (1 mg/kg each, namely D1V1) than those injected with lipoDox plus VNB (1 mg/kg each, namely D1fV1). No severe side effects were detected in each group. The tumor-to-muscle ratio (T/M) derived from 3'-dexoy-3'-[18F]fluorothymidine ([18F]FLT) micro positron emission tomography (PET) images of D1V1- and D1fV1-treated mice and the controls on day 7 was 6.88 ± 0.54, 7.50 ± 0.84, and 9.87 ± 0.73, respectively, suggesting that D1V1 is a more efficacious regimen against CT-26 xenografts. The results of proliferating cell nuclear antigen (PCNA) immunohistochemical staining were consistent with those findings obtained from [18F]FLT microPET imaging. CONCLUSION: This study demonstrated that lipoDox in combination with lipoVNB was more efficacious than clinically used regimen, lipoDox plus VNB, in the treatment of colon carcinoma and [18F]FLT-PET is a promising approach in monitoring the treatment outcome at early stage.
Authors: A Carrato; R Rosell; C Camps; A Antón; R García-Gómez; E Aranda; B Massutí; N Díaz-Fernández; J J Sánchez; M L García-Paredes Journal: Lung Cancer Date: 1997-07 Impact factor: 5.705
Authors: David Cunningham; Wendy Atkin; Heinz-Josef Lenz; Henry T Lynch; Bruce Minsky; Bernard Nordlinger; Naureen Starling Journal: Lancet Date: 2010-03-20 Impact factor: 79.321
Authors: Ulrike Seitz; Martin Wagner; Bernd Neumaier; Edgar Wawra; Gerhard Glatting; Gerhard Leder; Roland M Schmid; Sven N Reske Journal: Eur J Nucl Med Mol Imaging Date: 2002-06-04 Impact factor: 9.236