Radioisotopes in biology
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radioisotopes potential in biology
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Radioisotopes in biology
- 2. INTRODUCTION HISTORY PHENOMENON OF RADIATION RADIOISOTOPES IN BIOLOGY SCOPE DISADVANTAGES CONCLUSION
- 3. ISOTOPES Having same atomic number (protons in nucleus) and different atomic mass ( proton + neutron) . STABLE ISOTOPES Stable nuclei and do not undergo radioactive decay. RADIOISOTOPES Unstable isotopes which through the process of the radioactive decay attain stability. RADIOACTIVE DECAY Particles or electromagnetic radiation are emitted from the nucleus of an unstable isotope.
- 4. Wilhelm Röntgen 1895, produced and detected X-rays Henri Becquerel, 1896 discovered Radioactivity Marie and Perrie Curie, 1898 discovery of Polonium and Radium.
- 5. THE ATOM • Protons(P) in nucleus indicates the atomic number(Z) of the element. • Central nucleus is of proton (P) and neutrons(N) where atomic mass (A) is concentrated. [A= Z+N] Atomic stability and radiation • Ratio of neutrons to proton determine the stability of the elements ELEMENTS With low Z With high Z N/P N/P
- 6. P N CONT.. Isotopes having high Z are unstable as nuclear binding energy decreases for the protons. Instability of isotopes leads to radioactive decay. Radiatioactive decays are classified as • Alpha (α), Beta (β),Gamma (ϒ) and X Ray radiation.
- 7. ALPHA Heavy Charged particle Most Toxic Constant energy per particle BETA Light Charged Particle Less toxic Negatively charged Energy varies particle to particle GAMMA/ X RAY Electromagnetic Radiation Toxicity same as β Highly penetrating PENETRATION DIAGRAM
- 8. TERMS AND UNITS • Half-life Time taken for the activity to fall from any value to half of that value • Biological half-life Time taken by half the amount of radioisotopic element to leave the body. • Bq- One disintegration per second (dps) • Ci- Disintegration in 1g Radium (curie - 3.7x1010 disintegration per seconds) • Sv - Amount of radiation that gives a dose in humans equivalent to 1Gy of X-ray (1Gy=100 rad; 1 rad = .01j/kg
- 9. Radioisotopes -exquisite sensitivity Radiotracing a process Compatibility with in vivo system Assays and Probe
- 10. • For metabolic pathway elucidation • Metabolic turn over time • Pharmacological studies
- 11. • Detection and localization of radiation from a given object. • Photographic emulsion- silver halide + gel • Ionising radiation from radioactive object acts upon photographic emulsion to give latent image. • Radioactive event- Dark silver grains • Uses- i. Detection on chromatogram ii. Tissue/organ sections iii. DNA,RNA and protein studies
- 12. • Radioimmunoassay (RIA) is sensitive technique used to measure concentrations of antigens by use of antibodies • Principle: Competitive binding of radiolabeled Ag* and unlabeled Ag to a high-affinity Ab
- 13. A STEPS IN RIA B. Determination of Uk C. EXAMPLE
- 14. Historical perspective of 32 P & 35S - Hershey and Chase experiment Use of 32 P and 3H Probes and Labeling Probes 20-30 ntd* End labeling 5’ or 3’
- 16. MISMATCH CLEAVAGE ASSAY Radiolabelled synthetic RNA strands • Method used to detect point mutation and genomic variations. • Synthetic wild type isotopic RNA forms heteroduplex with cDNA of mutated gene • RNAse cleaves to the mismatch points in the heteroduplex • PAGE analysis gives insight of the point mutations. • Used in cancer research and vaccines production. eg. P 53 gene Isotopic RNA cDNA from mutated mRNA Heteroduplex RNAse Proc. Natl. Acad. Sci. USA Vol. 87, pp. 7555-7559,Iternational Atomic Energy Agency
- 17. • Efficacious therapy of diseases by noninvasive manner • Radioisotopes – 131 I , 211 At, 192Ir • Eg. Hyperthyroidism and cancers.
- 18. POSITRON EMISSION TOMOGRAPHY 3D image of functional processes in the body. •Radioisotopes and radio tracers - nitrogen-13 ,oxygen 15 ,fluorine- 18 Eg.18- FDG •Positron decay produces indirect gamma rays. •Detection- Gamma camera in the scanner •USES •Clinical diagnosis •Neuroimaging
- 19. •RADISOTOPES- 60Co , 192Ir , 137Cs •EXTERNAL BEAM RADIATION THERAPY •INTERNAL BEAM RADIATION THERAPY(BRACHYTHERAPY) EBRT IBRT
- 20. CONVENTIONAL RI • Conjugation of Ab with radionuclide • Eg.90 Y , 131I, 161Tb • AUGER THERAPY • 125 I, 177Lu • Low energy electron (Auger Electrons) emission. • Highly accurate, less damaging and applicable with non-internalizing Abs. ACCR ; Institut Laue-langevin
- 21. • EVOLUTIONARY AND ARCHELOGICAL SCIENCE- RADIODATING • CRIMNOLOGY AND HISTORY- NEUTRON ACTIVATION ANALYSIS • AGRICULTURE , ENVIRONMENT & ECONOMICS Radiolabeled pesticides Crop improvement- BARC(2010) green gram, black gram, groundnut, jute FROM WHERE DID THE ICE MAN COMMETH ? WHO KILLED NAPOLEAN?
- 22. • Damage to environment and disposal problems. • High cost for production of radioisotopes. • Radiation induced mutations or other health issues. • In assays or detections possibility of loss of native state of sample.
- 23. • Radioisotopes are aiding in the developmental researches and disease profiling. • Radio tracing opened avenues for in-vivo processes’s elucidation • Development of Molecular Biology • In Nuclear medicine diagnostic and therapeutics radiopharmaceuticals aiding treatments by non invasive method.
- 24. THANK YOU!
Editor's Notes
- . The antigen is generally labeled with a gamma-emitting isotope such as 125I, but beta-emitting isotopes such as tritium (3H) are also routinely used as labels. The radiolabeled antigen is part of the assay mixture; the test sample may be a complex mixture, such as serum or other body
- Spectroscopic techniques in radioisotopics detction?
- computer simulations which provide a simple estimator of genetic distances from the comparison of RNAse A digestion patterns. The results show that the number of non-shared fragments is proportional to the number of mutations between each pair of sequences .
- The amounts of I-131 used to ablate residual thyroid tissue have varied over a wide range. The use of "fixed" mCi amounts (eg, 100 mCi or 30 mCi for all patients)
- Two other PET imaging tracers, florbetapir and flutemetamol.. florbetaben F18 injection Technetium-99m is a metastable nuclear isomerof technetium-99 Technetium-99m when used as a radioactive tracer can be detected in the body by medical equipment (gamma cameras). ts biological half-life of 1 dayallows for scanning procedures which collect data rapidly but keep total patient radiation exposure low. The same characteristics make the isotope suitable only for diagnostic but never therapeutic use. (11 to 30 mCi) As the radioisotope undergoes positron emission decay (also known as positive beta decay), it emits a positron, an antiparticle of the electron with opposite charge. The emitted positron travels in tissue for a short distance (typically less than 1 mm, but dependent on the isotope[11]), during which time it loses kinetic energy, until it decelerates to a point where it can interact with an electron.[12] The encounter annihilates both electron and positron, producing a pair of annihilation (gamma)photons moving in approximately opposite directions. These are detected when they reach a scintillator in the scanning device, creating a burst of light which is detected by photomultiplier tubes or siliconavalanche photodiodes (Si APD). The technique depends on simultaneous or coincident detection of the pair of photons moving in approxima This limitation restricts clinical PET primarily to the use of tracers labelled with fluorine-18, which has a half-life of 110 minutes and can be transported a reasonable distance before use A typical dose of FDG used in an oncological scan has an effective radiation dose of 14 mSv Alzheimer's disease greatly decrease brain metabolism of both glucose and oxygen in tandem, standard FDG-PET of the brain, which measures regional glucose use, may also be successfully used to differentiate Alzheimer's disease from other dementing processes, and also to make early diagnosis of Alzheimer's disease. The advantage of FDG-PET for these uses is its much wider availability. PET imaging with FDG can also be used for localization of seizure focus: A seizure focus will appear as hypometabolic during an interictal scan. Several radiotracers (i.e. radioligands) have been developed for PET that are ligands for specific neuroreceptor subtypes such as [11C] raclopride, [18F] fallypride and [18F] desmethoxyfallypride for dopamine D2/D3 receptors, [11C]McN 5652 and [11C] DASB for serotonin transporters, [18F] Mefway for serotonin 5HT1A receptors, [18F] Nifene for nicotinic acetylcholine receptors or enzyme substrates (e.g. 6-FDOPA for the AADC enzyme). These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses. The development of a number of novel probes for noninvasive, in vivo PET imaging of neuroaggregate in human brain has brought amyloid imaging to the doorstep of clinical use. The earliest amyloid imaging probes included 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP)[30] developed at the University of California, Los Angeles and N-methyl-[11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole[31] (termed Pittsburgh compound B) developed at the University of Pittsburgh. These amyloid imaging probes permit the visualization of amyloid plaques in the brains of Alzheimer's patients and could assist clinicians in making a positive clinical diagnosis of AD pre-mortem and aid in the development of novel anti-amyloid therapies. [11C]PMP (N-[11C]methylpiperidin-4-yl propionate) is a novel radiopharmaceutical used in PET imaging to determine the activity of the acetylcholinergic neurotransmitter system by acting as a substrate for acetylcholinesterase. Post-mortem examination of AD patients have shown decreased levels of acetylcholinesterase. [11C]PMP is used to map the acetylcholinesterase activity in the brain, which could allow for pre-mortem diagnosis of AD and help to monitor AD treatments.[32] Avid Radiopharmaceuticals of Philadelphia has developed a compound called 18F-AV-45 that uses the longer-lasting radionuclide fluorine-18 to detect amyloid plaques using PET scans.[33] wo 511 keV gamma
- C0 60 – gamma rays… beam energy of 1.25 MeV Synthetic isotopes heavier than 191 decay by β− decay, although 192Ir also has a minor electron capture decay path
- If no antigen on surface? If no internalisation? - AT
- Several steps were taken by the FAO and IAEA division in close cooperation with the World Health Organization (WHO) to promote international acceptance of irradiated food (WHO, 1988). The Joint FAO/IAEA/WHO Expert Committees on the Wholesomeness of Irradiated Food (1980) have evaluated the safety of irradiated foods for human consumption and concluded that the irradiation of any food up to an average dose of 10 kGy causes no toxicological hazard. Irradiation of food is controversial in many parts of the world (Diehl, 1993). World-wide introduction of food irradiation is necessary to enhance confidence among trading nations that foods irradiated in one country and offered for sale in another, have been subjected to commonly acceptable standards of wholesomeness, hygienic practice, and irradiation treatment control. Efforts and support from international organizations, governments, and the food industry will be needed for the introduction of food irradiation on a truly commercial scale (Diehl, 1990). Some organizations and industries do not recognize this cheap and efficient food preservation method. In the last 30 years of testing of irradiated foods, no harmful effects to animals or humans have been found so now attitude of relevant organizations is changing and some irradiated foods are being released for general consumption. Many countries have accorded clearance for gamma irradiation of food items. The ttle use for younger bones. To date more recent remains, Black is using isotopes with shorter half-lives than carbon-14. He has found that the most useful are lead-210 and polonium-210, with half-lives of 22 years and 134 days respectively. These and other elements entering our bones are primarily from food, so Black can also use his measurements to sketch the victim's diet. A depletion of certain elements will reveal if the person was a vegetarian, for example FDG-97
- s.