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9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...
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9. DIAGNOSTIC NUCLEAR MEDICINE 9.1. RADIOPHARMACEUTICALS FOR ...

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  • 1. Nuclear imaging produces images of theNuclear imaging produces images of the distribution of radionuclide in patients.distribution of radionuclide in patients. Method of administration:Method of administration: Injection (appropriate for organ)Injection (appropriate for organ) How to determine distributionHow to determine distribution Blood volume/flow/organ uptakeBlood volume/flow/organ uptake What type of radionuclides?What type of radionuclides? X-rays emittersX-rays emitters γγ-ray emitters-ray emitters (charged particles are absorbed by body tissue)(charged particles are absorbed by body tissue) How to detect?How to detect? Photon detectionPhoton detection
  • 2. There are several techniques for nuclear imaging:There are several techniques for nuclear imaging: Static planar scintigraphy which providesStatic planar scintigraphy which provides two-dimensionaltwo-dimensional representations of a three dimensional objectrepresentations of a three dimensional object by measuring theby measuring the spatial distribution of the radioisotope in the body, (comparablespatial distribution of the radioisotope in the body, (comparable to a plain X-ray projection).to a plain X-ray projection). Dynamic planar scintigraphy which measures temporalDynamic planar scintigraphy which measures temporal changes in the spatial distribution of the radioisotopes in thechanges in the spatial distribution of the radioisotopes in the body, by takingbody, by taking multiple images over periods of time whichmultiple images over periods of time which may vary from milliseconds to hours depending on themay vary from milliseconds to hours depending on the timescale for the basic function of the organ to be examined.timescale for the basic function of the organ to be examined. Single photon emission tomography (SPECT) or positronSingle photon emission tomography (SPECT) or positron emission tomography (PET)emission tomography (PET) which allows to form threewhich allows to form three dimensional static or dynamic representations of the organ anddimensional static or dynamic representations of the organ and organ functions by taking multiple images from differentorgan functions by taking multiple images from different directions.directions.
  • 3. The great advantage of nuclear medicine is itsThe great advantage of nuclear medicine is its ability to image qualitatively and quantitativelyability to image qualitatively and quantitatively dynamic physiological processes of different bodydynamic physiological processes of different body organs.organs. To highlight a particular organ the radioisotope must beTo highlight a particular organ the radioisotope must be administered in the form of a chemical agentadministered in the form of a chemical agent (radiopharmaceutical) which addresses preferably a particular(radiopharmaceutical) which addresses preferably a particular organ (e.g. iodine in thyroid) or the physiological function of aorgan (e.g. iodine in thyroid) or the physiological function of a particular organ (e.g. blood flow).particular organ (e.g. blood flow). Therefore a radiopharmaceutical is typically made of twoTherefore a radiopharmaceutical is typically made of two components, thecomponents, the radionuclide and the chemical compoundradionuclide and the chemical compound toto which it is bound.which it is bound. Since radiopharmaceuticals are used to study body functions,Since radiopharmaceuticals are used to study body functions, it is important that they have no pharmacological orit is important that they have no pharmacological or toxicological effects which may interfere with the organ functiontoxicological effects which may interfere with the organ function under study. Therefore the pharmaceutical is administered inunder study. Therefore the pharmaceutical is administered in extremely small amounts (10extremely small amounts (10-9-9 g).g).
  • 4. A number of factors is responsible for theA number of factors is responsible for the ultimate distribution of the radioisotope:ultimate distribution of the radioisotope: blood flowblood flow (percent cardiac input/output of a specific organ)(percent cardiac input/output of a specific organ) availability of compound to tissue, or the proportionavailability of compound to tissue, or the proportion of the tracer that is bound to proteins in the bloodof the tracer that is bound to proteins in the blood basic shape, size, and solubility of molecule whichbasic shape, size, and solubility of molecule which controls its diffusion capabilities through bodycontrols its diffusion capabilities through body membranesmembranes
  • 5. The final fate of the radiotracer depends on how theThe final fate of the radiotracer depends on how the addressed organ deals with the molecule, whether itaddressed organ deals with the molecule, whether it is absorbed, broken down byis absorbed, broken down by intracellular chemicalintracellular chemical processes or whether it exits from the cells and isprocesses or whether it exits from the cells and is removed by kidney or liver processes. Theseremoved by kidney or liver processes. These processes determine theprocesses determine the biological half-lifebiological half-life TTBB of theof the radiopharmaceutical (half-liferadiopharmaceutical (half-life ≡≡ time to reducetime to reduce material to 50% of its initial amount).material to 50% of its initial amount). To design and administer a radiopharmaceutical withTo design and administer a radiopharmaceutical with specific localizing properties all these functions as well asspecific localizing properties all these functions as well as the choice of radionuclide has to be taken into account.the choice of radionuclide has to be taken into account.
  • 6. The choice of the appropriate radioisotope forThe choice of the appropriate radioisotope for nuclear imaging is dictated by the physicalnuclear imaging is dictated by the physical characteristics of the radioisotope:characteristics of the radioisotope: a suitable physical half-life; long enough for monitoring thea suitable physical half-life; long enough for monitoring the physiological organ functions to be studied, but not too long tophysiological organ functions to be studied, but not too long to avoid long term radiation effectsavoid long term radiation effects decay via photo emission (X-ray ordecay via photo emission (X-ray or γγ-ray) to minimize absorption-ray) to minimize absorption effects in body tissueeffects in body tissue photon must have sufficient energy to penetrate body tissue withphoton must have sufficient energy to penetrate body tissue with minimal attenuationminimal attenuation but photon must have sufficiently low energy to be registeredbut photon must have sufficiently low energy to be registered efficiently in detector and to allow the efficient use of leadefficiently in detector and to allow the efficient use of lead collimator systems (must be absorbed in lead)collimator systems (must be absorbed in lead) decay product (daughter) should have minimal short-lived activitydecay product (daughter) should have minimal short-lived activity
  • 7. The effective half-lifeThe effective half-life TTEE of a radiopharmaceutical is aof a radiopharmaceutical is a combination of the physical half-lifecombination of the physical half-life TT1/21/2 and theand the biological half-lifebiological half-life TTBB :: The effective half-life of radiopharmaceuticalsThe effective half-life of radiopharmaceuticals containing a long lived radioisotope can be reducedcontaining a long lived radioisotope can be reduced by choosing a chemical component with a shortby choosing a chemical component with a short biological half-life.biological half-life. A close matching of the effective half-life with theA close matching of the effective half-life with the duration of the study is important for dosimetricduration of the study is important for dosimetric considerations. It also is important as far as theconsiderations. It also is important as far as the availability and expense of the radiopharmaceutical isavailability and expense of the radiopharmaceutical is concerned.concerned.
  • 8. Radioisotopes in common use are:Radioisotopes in common use are: 9999 TcTcmm (T(T1/21/2=6.02h, E=6.02h, Eγγ=140 keV) is used in more=140 keV) is used in more than 70% of all medical applicationsthan 70% of all medical applications 226226 Ra (TRa (T1/21/2=1600 a, E=1600 a, Eγγ=186 keV) is an=186 keV) is an αα-emitter-emitter ((αα's are absorbed in body tissue), is used for's are absorbed in body tissue), is used for highly localized studieshighly localized studies 6767 Ga (TGa (T1/21/2=78.3h, E=78.3h, Eγγ =93 keV, 185 keV, 300=93 keV, 185 keV, 300 keV) is often used as tumor localizing agentkeV) is often used as tumor localizing agent (gallium citrate)(gallium citrate)123123 I (TI (T1/21/2=13h, E=13h, Eγγ=159 keV) bonds good=159 keV) bonds good with proteins and molecules that can bewith proteins and molecules that can be iodinated. It has replacediodinated. It has replaced 131131 I (TI (T1/21/2=6d, E=6d, Eγγ=364=364 keV) because of the reduced radiationkeV) because of the reduced radiation exposureexposure8181 KrKrmm (T(T1/21/2=13s, E=13s, Eγγ=190 keV) is a very short-=190 keV) is a very short- lived gas used to perform lung ventilationlived gas used to perform lung ventilation studies, (short half-life limits its application)studies, (short half-life limits its application)
  • 9. Important forImportant for PETPET studies are neutron deficient isotopesstudies are neutron deficient isotopes which decay by positron emission. Positrons annihilate withwhich decay by positron emission. Positrons annihilate with electrons emitting two Eelectrons emitting two Eγγ=511 keV photons in opposite=511 keV photons in opposite direction.direction. Currently used positron emitters are:Currently used positron emitters are: 6868 Ga (TGa (T1/21/2=68 m, E=68 m, Eγγ= 511 keV)= 511 keV) 8282 Rb (TRb (T1/21/2=1.3 m, E=1.3 m, Eγγ = 511 keV)= 511 keV) 1818 F (TF (T1/21/2=110 m, E=110 m, Eγγ = 511 keV), (used in more than 80% of= 511 keV), (used in more than 80% of all PET applications)all PET applications) 1313 N (TN (T1/21/2=10 m, E=10 m, Eγγ = 511 keV)= 511 keV) 1111 C (TC (T1/21/2=20.4 m, E=20.4 m, Eγγ = 511 keV)= 511 keV) Most of the positron emitters are still being studied inMost of the positron emitters are still being studied in terms of their applicability for diagnostic purposes.terms of their applicability for diagnostic purposes.
  • 10. The production of radioisotopes is expensive!The production of radioisotopes is expensive! It is based on four different methods:It is based on four different methods: nuclear fission (reactor breeding)nuclear fission (reactor breeding) neutron activation processesneutron activation processes charged particle induced reactionscharged particle induced reactions radionuclide generator (chemical method)radionuclide generator (chemical method) Each method provides useful isotopes withEach method provides useful isotopes with differing characteristics for nuclear imaging.differing characteristics for nuclear imaging.
  • 11. Nuclear Fission: In nuclear fission, the nuclei of atoms are split, causing energy to be released. The atomic bomb and nuclear reactors work by fission. The element uranium is the main fuel used to undergo nuclear fission to produce energy since it has many favorable properties. Uranium nuclei can be easily split by shooting neutrons at them. Also, once a uranium nucleus is split, multiple neutrons are released which are used to split other uranium nuclei. This phenomenon is known as a chain reaction.
  • 12. NUCLEAR FISSIONNUCLEAR FISSION takes place in the reactor coretakes place in the reactor core and is induced by the slow neutron induced fissionand is induced by the slow neutron induced fission (break-up) of(break-up) of 235235 U into medium mass nuclei.U into medium mass nuclei. The most common radioisotopes produced by fission (withThe most common radioisotopes produced by fission (with subsequent isotope separation based on different physicalsubsequent isotope separation based on different physical and chemical methods) areand chemical methods) are 9999 MoMo (which decays to(which decays to 9999 TcTcmm ),), 131131 II,, andand 133133 XeXe!!
  • 13. NEUTRON ACTIVATIONNEUTRON ACTIVATION is based on captureis based on capture reactions of thermal neutrons (produced in the reactorreactions of thermal neutrons (produced in the reactor as consequence of the fission process) on stableas consequence of the fission process) on stable isotopes which are positioned near the reactor core.isotopes which are positioned near the reactor core. Examples for radioisotope production via neutron capture are:Examples for radioisotope production via neutron capture are: • 9898 Mo + nMo + n →→ 9999 Mo +Mo + γγ • 5050 Cr + nCr + n →→ 5151 Cr +Cr + γγ • 3131 P + nP + n →→ 3232 P +P + γγ • 3232 S + nS + n →→ 3232 P + pP + p The yieldThe yield NNrr for the radioisotope production over thefor the radioisotope production over the time periodtime period tt depends on the cross sectiondepends on the cross section σσ [cm[cm22 ] of] of the neutron capture process, the neutron-fluxthe neutron capture process, the neutron-flux φφ [cm[cm-2-2 ss-- 11 ], the number of target nuclei], the number of target nuclei nnTT, and the decay, and the decay constantconstant λλ = ln2/T= ln2/T1/21/2
  • 14. The table shows several radioisotopes produced byThe table shows several radioisotopes produced by neutron absorption.neutron absorption. Disadvantage is that the produced radioisotope isDisadvantage is that the produced radioisotope is typically an isotope of the target element, thereforetypically an isotope of the target element, therefore chemical separation is not possible. This means that thechemical separation is not possible. This means that the (n,(n,γγ) produced radionuclide are not carrier-free.) produced radionuclide are not carrier-free. 1 barn = 10-24 cm2
  • 15. CHARGED PARTICLE INDUCED REACTIONSCHARGED PARTICLE INDUCED REACTIONS areare based on the use of accelerators. Charged particlesbased on the use of accelerators. Charged particles like protons, deuterons or alphas are accelerated tolike protons, deuterons or alphas are accelerated to energies between 1 to 100 MeV and bombard a targetenergies between 1 to 100 MeV and bombard a target material.material. The most used accelerator type is the cyclotron, whereThe most used accelerator type is the cyclotron, where the charged particles are accelerated by oscillatingthe charged particles are accelerated by oscillating accelerating potentials perpendicular to a deflectingaccelerating potentials perpendicular to a deflecting magnetic field.magnetic field.
  • 16. Examples of typical reactions in the target are listed inExamples of typical reactions in the target are listed in the tablethe table The advantage of production via charge particleThe advantage of production via charge particle interaction is the large difference in Z between theinteraction is the large difference in Z between the target material and the radionuclide. That allows goodtarget material and the radionuclide. That allows good physical and chemical separation procedures.physical and chemical separation procedures.
  • 17. RADIONUCLIDE GENERATORSRADIONUCLIDE GENERATORS allow to separate chemically short-allow to separate chemically short- lived radioactive daughter nuclei with good characteristics for medicallived radioactive daughter nuclei with good characteristics for medical imaging from long-lived radioactive parent nuclei. Typical techniquesimaging from long-lived radioactive parent nuclei. Typical techniques used are chromatographic absorption, distillation or phase separation.used are chromatographic absorption, distillation or phase separation. This method is in particular applied for the separation of the rather short-This method is in particular applied for the separation of the rather short- livedlived 9999 TcTcmm (T(T1/21/2=6 h) from the long lived=6 h) from the long lived 9999 Mo (TMo (T1/21/2=2.7 d).=2.7 d). Applying the radioactive decay law the growth of activity of the daughterApplying the radioactive decay law the growth of activity of the daughter nuclei Anuclei A22 with respect of the initial activity of the mother nucleuswith respect of the initial activity of the mother nucleus AA11 00 cancan be expressed in terms of their respective decay constantsbe expressed in terms of their respective decay constants λλ22 andand λλ22 withwith λλ22 >>>> λλ11:: Milking cow analogy
  • 18. Radionuclide Generator system used to generate a radionuclide for routine clinical practice. The most widely used generator system is the molybdenum- 99/technetium-99m generator on which much of current routine nuclear imaging relies. In this generator, the mother nuclide Mo-99 decays into the daughter nuclide Tc-99m with a half life of 2.7 days, which itself has a half life of 6 hours (technetium (Tc) (I), Fig. 1). Other generator systems have been built, among them a Sr-82/Rb82 generator for PET imaging, with Rb82 having a half-life of 2 minutes and behaving like thallium Tl and a Rb-81/Kr81m generator which yields a short- lived (13 s) krypton Kr gas for ventilation studies. These generator systems are so expensive that their clinical use is only feasible in centers with a very large patient throughput.
  • 19. In a generator such as the Mo-99/Tc-99m radionuclide generator in which the half-life of the mother nuclide is much longer than that of the daughter nuclide, 50% of equilibrium activity is reached within one daughter half-life, 75% within two daughter half-lives. Hence, removing the daughter nuclide from the generator ("milking" the generator) is reasonably done every 6 hours or, at most, twice daily in a Mo-99/Tc-99m generator. Most commercial Mo-99/Tc-99m generators use column chromatography, in which Mo-99 is adsorbed onto alumina. Pulling normal saline through the column of immobilized Mo-99 elutes the soluble Tc-99m, resulting in a saline solution containing the Tc-99m which is then added in an appropriate concentration to the kits to be used. The useful life of a Mo-99/Tc-99m generator is about 3 half lives or approximately one week. Hence, any clinical nuclear medicine units purchase at least one such generator per week or order several in a staggered fashion.
  • 20. The table lists typical generator produced radionuclide.The table lists typical generator produced radionuclide.

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