Pharmacokinetic Parameters and Biodistribution of Soluble Cytokine Receptors

Publisher Summary This chapter discusses the pharmacokinetic parameters and biodistribution of soluble cytokine receptors. In a study described in the chapter, for pharmacokinetic and biodistribution analysis, radiolabeled soluble receptors were evaluated as monomers and as dimers in the form of fusion proteins in some cases. Because interleukin-1 receptor (IL-IR) and interleukin-4 receptor (IL-4R) are species-specific, monomeric forms of soluble mouse IL-IR and mouse IL-4R were used in the studies. Both IL-IR and the IL-4R were produced in HeLa cells. An IL-4R fusion protein containing two soluble mouse IL-4R monomers on a mouse IgG 2 b Fc structure was also evaluated. Various forms of soluble human tumor necrosis factor receptor (TNF-R) were also analyzed in mice because human TNF-R can bind either murine TNF- α or TNF- β . Two forms of monomeric TNF-R were evaluated: an unglycosylated form produced by an Escherichia coli expression system and a glycosylated form produced by a CHO expression system.