The physical chemistry of ligand-receptor binding identifies some limitations to the analysis of receptor images

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13 Citations (Scopus)

Abstract

The biophysical chemistry of ligand-receptor interactions imposes some restrictions on the characteristics of a radioligand if it is to be a useful tracer for accurately measuring the in vivo concentration of a specific cellular membrane receptor. This review discusses thermodynamic and kinetic rate constant considerations in selecting a ligand for radiolabeling and imaging. When radioligands of only modest specific activity are injected, one is able to use kinetic analysis to calculate the rate constant for the bimolecular binding reaction as well as the receptor concentration. Images of regional receptor density can be constructed from analysis of emission imaging data when the binding occurs at a rate that is slower than the collision frequency. A tracer that reacts with each collision cannot distinguish receptor density from blood flow. The theory of diffusion-limited reactions is reviewed and individual ligand-receptor examples are presented to demonstrate conditions where, even for very fast forward reactions, the binding of radioligand to receptor is controlled by local biochemistry rather than by the purely physical process of diffusion.

Original languageEnglish (US)
Pages (from-to)477-483
Number of pages7
JournalNuclear Medicine and Biology
Volume28
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

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Physical Chemistry
Ligands
Physical Phenomena
Thermodynamics
Biochemistry
Membranes

Keywords

  • β-adrenergic ligands
  • Diffusion
  • Epidermal growth factor
  • Kinetic modeling
  • Ligand-receptor thermodynamics
  • Superoxide dismutase

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

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abstract = "The biophysical chemistry of ligand-receptor interactions imposes some restrictions on the characteristics of a radioligand if it is to be a useful tracer for accurately measuring the in vivo concentration of a specific cellular membrane receptor. This review discusses thermodynamic and kinetic rate constant considerations in selecting a ligand for radiolabeling and imaging. When radioligands of only modest specific activity are injected, one is able to use kinetic analysis to calculate the rate constant for the bimolecular binding reaction as well as the receptor concentration. Images of regional receptor density can be constructed from analysis of emission imaging data when the binding occurs at a rate that is slower than the collision frequency. A tracer that reacts with each collision cannot distinguish receptor density from blood flow. The theory of diffusion-limited reactions is reviewed and individual ligand-receptor examples are presented to demonstrate conditions where, even for very fast forward reactions, the binding of radioligand to receptor is controlled by local biochemistry rather than by the purely physical process of diffusion.",
keywords = "β-adrenergic ligands, Diffusion, Epidermal growth factor, Kinetic modeling, Ligand-receptor thermodynamics, Superoxide dismutase",
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