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Journal of Nuclear Medicine Vol. 50 No. 12 2073-2081
© 2009 by Society of Nuclear Medicine
doi: 10.2967/jnumed.109.063503

Basic Science Investigation

Therapeutic Efficacy Evaluation of 111In-Labeled PEGylated Liposomal Vinorelbine in Murine Colon Carcinoma with Multimodalities of Molecular Imaging

Tong-Hsien Chow1, Yi-Yu Lin1, Jeng-Jong Hwang1, Hsin-Ell Wang1, Yun-Long Tseng2, Victor Fei Pang3, Ren-Shyan Liu4, Wuu-Jyh Lin5, Chung-Shi Yang6 and Gann Ting6

1 Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; 2 Taiwan Liposome Company, Taipei, Taiwan; 3 Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; 4 Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 5 Institute of Nuclear Energy Research, Taoyuan, Taiwan; and 6 National Health Research Institute, Taipei, Taiwan

Correspondence: For correspondence or reprints contact: Jeng-Jong Hwang, Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 155 Li-Nong St., Section 2, Pei-tou, Taipei 112, Taiwan. E-mail: jjhwang{at}ym.edu.tw

In our previous studies using combined radioisotopes with chemotherapeutic liposomal drugs (i.e., 111In-labeled polyethylene glycol (PEG)ylated liposomal vinorelbine) we have reported possible therapeutic efficiency in tumor growth suppression. Nevertheless, the challenge remains as to whether this chemotherapy has a therapeutic effect as good as that of combination therapy. The goal of this study was to investigate the real therapeutic effectiveness of 6 mol% PEG 111In-vinorelbine liposomes via the elevation of the radiation dosage and reduction in the concentration of chemotherapeutic agents. Methods: Murine colon carcinoma cells transfected with dual-reporter genes (CT-26/tk-luc) were xenografted into BALB/c mice. The biodistribution was estimated to determine the drug profile and targeting efficiency of 111In-vinorelbine liposomes. Bioluminescence imaging and 18F-FDG small-animal PET were applied to monitor the therapeutic response after drug administration. The survival in vivo was estimated and linked with the toxicologic and histopathologic analyses to determine the preclinical safety and feasibility of the nanomedicine. Results: Effective long-term circulation of radioactivity in the plasma was achieved by 6 mol% PEG 111In-vinorelbine liposomes, and this dose showed significantly lower uptake in the reticuloendothelial system than that of 0.9 mol% PEG 111In-vinorelbine liposomes. Selective tumor uptake was represented by cumulative deposition, and the maximum accumulation was at 48 h after injection. The combination therapy exhibited an additive effect for tumor growth suppression as tracked by caliper measurement, bioluminescence imaging, and small-animal PET. Furthermore, an improved survival rate and reduced tissue toxicity were closely correlated with the toxicologic and histopathologic results. Conclusion: The results demonstrated that the use of 6 mol% PEG 111In-vinorelbine liposomes for passively targeted tumor therapy displayed an additive effect with combined therapy, not only by prolonging the circulation rate because of a reduction in the phagocytic effect of the reticuloendothelial system but also by enhancing tumor uptake. Thus, this preclinical study suggests that 6 mol% PEG 111In-vinorelbine liposomes have the potential to increase the therapeutic index and reduce the toxicity of the passively nanotargeted chemoradiotherapies.

Key Words: 111In-vinorelbine liposomes • CT-26/tk-luc • bioluminescence imaging (BLI) • 18F-FDG small-animal PET • reticuloendothelial system (RES)

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.


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