The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs

Nucl Med Biol. 2005 Feb;32(2):157-64. doi: 10.1016/j.nucmedbio.2004.11.003.


Engineered multivalent single-chain Fv (scFv) constructs have been demonstrated to exhibit rapid blood clearance and better tumor penetration. To understand the short plasma half-life of multivalent single-chain antibody fragments, the pharmacokinetic properties of covalent dimeric scFv [sc(Fv)2], noncovalent tetrameric scFv {[sc(Fv)2]2} and IgG of MAb CC49 were examined. The scFvs displayed an ability to form higher molecular aggregates in vivo. A specific proteolytic cleavage of the linker sequence of the covalent dimeric or a deterioration of the noncovalent association of the dimeric scFv into tetravalent scFv constructs was not observed. In conclusion, sc(Fv)2 and [sc(Fv)2]2 are stable in vivo and have significant potential for diagnostic and therapeutic applications.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Neoplasm / genetics
  • Antibodies, Neoplasm / metabolism*
  • Cell Line, Tumor
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / radiotherapy
  • Female
  • Immunoglobulin Fragments / genetics
  • Immunoglobulin Fragments / metabolism*
  • Iodine Radioisotopes / pharmacokinetics*
  • Iodine Radioisotopes / therapeutic use
  • Metabolic Clearance Rate
  • Mice
  • Mice, Nude
  • Organ Specificity
  • Protein Engineering / methods*
  • Radioimmunotherapy / methods
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Tissue Distribution


  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • B72.3 antibody
  • Immunoglobulin Fragments
  • Iodine Radioisotopes
  • Radiopharmaceuticals