Radioimmunoassay (RIA)

Radioimmunoassay (RIA)

1. Definition, scope and place in clinical pharmacology

• Radioimmunoassay (RIA) is the original member of the immunoassay family — assays that exploit the specific molecular-recognition binding of antibodies (or other binding reagents) to capture, detect and measure an analyte — distinguished by the use of a radioactive label on the detection reagent (Atkinson 4e Ch.11, p.174).
• Immunoassays are equivalently termed ligand-binding assays (LBA); the two names are used interchangeably for this whole assay class, of which RIA is the radioisotopic prototype (Atkinson 4e Ch.11, p.174).
• The science of clinical pharmacology — both clinical practice (e.g. therapeutic drug monitoring to individualise a patient's dose) and drug development (selecting a safe, effective dose for a new pharmaceutical) — depends on the accurate, reliable measurement of drug, metabolite and/or biomarker concentrations in the relevant biological matrix; without reliable assays, applying clinical pharmacology to patient treatment or drug development is severely limited or impossible (Atkinson 4e Ch.11, p.169).
• Bioanalytical methods (RIA among them) are used to measure drug concentrations for pharmacokinetic and metabolic analyses, and to generate quantitative data for biomarkers — soluble proteins, systemic organic compounds, RNA/DNA fragments, even radiological images (Atkinson 4e Ch.11, p.169).
• Assays for drugs fall into two broad operational categories (Atkinson 4e Ch.11, p.169):
  • Developmental (pre-FDA-approval) assays — built to generate data supporting a new drug's behaviour and approval; once the drug is approved these assays are essentially "retired" and generally no longer used by the company.
  • "Patient-practice" assays — sometimes developed during drug development for use with the marketed drug in clinical practice; these include companion diagnostics and complementary diagnostic assays, and "standalone" diagnostic assays that identify, diagnose, or provide an action point for clinical intervention to guide patient treatment.
• Proving that such assays are reliable — validating them — has become a science in its own right; understanding RIA therefore means understanding both the platform and the validation strategy (Atkinson 4e Ch.11, p.169).