Characteristic Comparison Between 131I-Interferon-α and 131I-Interferon-α-Immunoglobulin-Fc Hybrid Protein in Rats Using Molecular Imaging.

ABSTRACT

BACKGROUND/AIM: Interferon-α (IFN-α) is produced to act locally and transiently with a relatively short circulation half-life in vivo. Hybridization of IFN-α with human immunoglobulin Fc, renamed as IFN-α-Fc, may overcome this limitation. In the present study, (131)I-IFN-α-Fc and (131)I-IFN-α were compared in the aspects of stability, pharmacokinetics, tissue distribution and molecular imaging quality in an animal model. MATERIALS AND METHODS: Both IFN-α-Fc and IFN-α were labelled with (131)I. Biodistributions and pharmacokinetics of both labelled proteins in Sprague-Dawley rats were assayed. Micro-single-photon emission computed tomography/computed tomography was used to non-invasively monitor the longitudinal distribution of both proteins. RESULTS: (131)I-IFN-α-Fc was shown to have higher stability than (131)I-IFN-α in whole blood, plasma, kidney, liver and stomach from the biodistribution study. The area under curve analyzed from plasma in the phomacokinetics study was 10-fold higher for (131)I-IFN-α-Fc than for (131)I-IFN-α. At 0-1 h post tail-vein injection, both labelled proteins are mainly accumulated in the kidneys and liver. Notably, (131)I-IFN-α-Fc is degraded more slowly than (131)I-IFN-α. CONCLUSION: We demonstrated that (131)I-IFN-α-Fc has longer blood circulation time and better biostability than (131)I-IFN-α, suggesting the potential application of the immunoglobulin Fc-conjugated cytokine for long-term treatment of diseases.