Historical Use of Radiotracers
The principle of radionuclides to track and follow physical, chemical and biological processes has achieved widespread use since their earliest discovery. The father of biological radiochemistry, George de Hevesy, was the first to use a radioactive isotope of lead in bone studies, closely followed by R. H. Stevens injecting radium chloride intravenously to study malignant lymphoma[14]. Artificially generated radioisotopes revolutionised the use of radiotracers in biomedical study[2]. Iodine radiosotopes have been used since the early 1940s to examine the thyroid gland[15]. Biodistribution studies of radiotracers in a subject began with the work of Cassen (rectilinear scanner)[16,17] and of the gamma scintillation …show more content…
Beginning with its discovery in 1940, radiocarbon 14C became the most useful tracer nuclide for organic molecules and biochemistry[19] simply by virtue of being an isotope of carbon and counting of the radioactive decays[20]. Natural background radiocarbon is produced continuously in the upper atmosphere and incorporated into biological systems through photosynthesis. Since the cessation of 14C intake occurs at death, measuring natural levels of radiocarbon in dead organic materials in conjunction with knowledge of the half-life (5730 years) and the rate of disintegrations per minute (DPM), permits the determination of the age of the material. Accelerator mass spectrometry (AMS) is the preferred mode of measuring the ratio of carbon isotopes in a sample and effectively counts ions of carbon at levels of attomole and zeptomole, which is approximately five orders of magnitude improvement achievable with radiometric assay. This sensitivity affords human metabolism studies to be conducted using 14C at radiochemical exposures that do not differ significantly from the …show more content…
The kinetics of transport were quantified using the pulse-chase of 14C labelled leucine[21]. However, the limitations on the yield of the radiosotopes for tracer studies meant that it was the advent of 99Mo/99mTc generator at Brookhaven National Laboratory (BNL) in 1957[22], which truly heralded the birth of modern nuclear medicine[23-25]. Wedded to molecular medicine and biochemistry, ‘omics’ technologies and clinical PET for cancer diagnosis, novel radiotracers can be developed which uniquely hone in on the pathology e.g. of carcinogenesis. Around the same time, modern radioimmunochemistry was used to detect and measure the levels of insulin in whole human plasma. The premise of the detection is simple, based upon a comparison of the inhibitory effect of an unlabelled antigen (measurand) on the binding of radioactive labelled antigen to a specific antibody with the inhibitory effect of known standards. Depending upon the specific activity of the radiotracer sub-picomolar detection limits have been attained. Yalow’s method has been adapted to measure the concentrations of vitamins, enzymes, peptides, serum proteins, hormones, viruses, drugs and tumour antigens[25].