title: Characteristic Comparison Between 131I-Interferon-α and 131I-Interferon-α-Immunoglobulin-Fc Hybrid Protein in Rats Using Molecular Imaging.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, R.O.C. Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan, Taiwan, R.O.C.
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Hsu
authors.affiliation: Department of Medical Imaging and Radiological Sciences, I-Shou University, Kaohsiung, Taiwan, R.O.C.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chien
authors.affiliation: Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan, Taiwan, R.O.C.
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Institute of Biologics, Development Center for Biotechnology, New Taipei City, Taiwan, R.O.C.
authors.forename: Ta-Tung
authors.initials: TT
authors.lastname: Yuan
authors.affiliation: Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan, Taiwan, R.O.C. jjhwang@ym.edu.tw twlee@iner.gov.tw.
authors.forename: Te-Wei
authors.initials: TW
authors.lastname: Lee
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, R.O.C. jjhwang@ym.edu.tw twlee@iner.gov.tw.
authors.forename: Jeng-Jong
authors.initials: JJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism*; D016898:Interferon-alpha / Q000378:metabolism* / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D055114:X-Ray Microtomography
chemical_list: D007141:Immunoglobulin Fc Fragments; D016898:Interferon-alpha; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins
keywords: 131I-IFN-α-Fc; biodistribution; micro-single-photon-emission computed tomography/computed tomography; pharmacokinetics