PRODUCTION OF RADIOPHARMACEUTICALS Gallium-68 generator
A gallium-68 generator is a device used to extract the positron-emitting isotope 68Ga of gallium from a source of decaying germanium-68. The parent isotope 68Ge has a half-life of 271 days and can be easily sent to hospitals within the generator, where it is storable for almost a year. Its decay product gallium-68 (with a half- life of only 68 minutes) is extracted and used for certain positron emission tomography nuclear medicine diagnostic procedures, where the radioisotope's relatively short half-life and emission of positrons for creation of 3-dimentional PET scans, are useful. Parent isotope (Ge-68) source
The parent isotope germanium-68 is the longest-lived (271 days) of the radioisotopes of germanium. It has been produced by several methods. In the U.S., it is primarily produced in proton accelerators:
At Brookhaven National Laboratories, 40 MeV proton irradiation of a gallium metal target produces germanium-68 by proton capture and double neutron knockout, from gallium-69 (the most common of two stable isotopes of gallium). This reaction is: Ga-69 + p --> 2n + Ge-68.
A Russian source produces germanium-68 from accelerator- produced helium ion (alpha) irradiation of zinc-66, again after knockout of two neutrons, in the nuclear reaction Zn-66 + alpha --> 2n + Ge-68. Mechanism of generator function
1. When loaded with the partent isotope germanium-68, these generators function similarly to technetium-99m generators, in both cases using a process similar to thin layer chromatography. The stationary phase is alumina onto which germanium- 68 is adsorbed. The mobile phase is a solvent able to elute (wash out) decayed germanium-68. 2. Currently Ga-68 (III) is easily eluted with a few mL of 1 M or 0.1M hydrochloric acid from generators, within 1 to 2 minutes. Conclusion: The PET isotope gallium-98 can be obtained from germanium-68 – gallium-68 generator. The parent germanium-68 prepared using 30-60 MeV energy and high current cyclotron has a long half life (271 days) and hence the generator can be transported over very long distances and useful for periods of up to one year.
Generator produced PET- radiopharmaceuticals
The availability of PET radionuclide generators would facilitate PET studies by those centres that do not have a cyclotron. In addition, it can also enhance the range of studies at existing cyclotron/PET centres.
Gallium-68 is finding use in cancer imaging when labelled with peptides.
The ultra short-lived rubidium-82 (a half-life of 75 seconds), available from a strontium-82 – rubidium-82 generator, and useful for PET imaging of blood flow to myocardium, Has high potential in managing heart patients. Characteristics of ideal generator system
1. If intended for clinical use, the output of the generator must .1 be sterile and pyrogen-free . 2. The chemical properties of the daughter must be different than those of the parent to permit separation of daughter from parent. Most often, separations are performed chromatographically . 3. Generator should be eluted with 0.9% saline solution and should involve no violent chemical reactions. . 4. Daughter isotope should be short-lived gamma-emitting nuclide (physical half-life = hrs-days).
5. Physical half-life of parent should be short enough so daughter regrowth after elution is rapid, but long enough for practicality
. 6. Daughter chemistry should be suitable for preparation of a wide variety of compounds, .especially those in kit form.
7. Very long-lived or stable granddaughter so no radiation dose is conferred to patient by decay of subsequent generations
8. Inexpensive, effective shielding of generator, minimizing radiation dose to those using it. 9. Easily recharged (we do NOT recharge Mo/Tc generators, but store them in decay areas after their useful life is over.
• The daughter activity grown by the decay of the parent is separated chemically from the parent. • The eluent in vial A is drawn through the column and the daughter nuclide is collected in vial B under vacuum.
Typical generator system The vial containing the eluant is first inverted onto needle A, and another evacuated vial is inverted onto the other needle B. Generator Activity Levels Production of Radionuclides Production 99 Mo/ commercial manufacturer on purchase technetium generators In practice, hospital pharmacies contamination and minimizes chances of radiation exposure personnelof a minimumto means that performed sterile The generators are supplied as a weekly standing 99 m Tc generator
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Faculty of Pharmacy – Assiut University – Fourth Year Elective Course - Radiopharmacy - 2010-2011 – 2nd sem Secular Equilibrium
Secular equilibrium: a condition reached when the tphys of the parent is many times greater than the tphys of the daughter, e.g., 100-1000 times greater. To keep things in perspective, during 10 half-lives of the daughter, decay of the parent is negligible. Decay of the parent is represented by the flat line in the diagram below. Transient Equilibrium
Transient equilibrium : a condition reached when the tphys of the parent is approximately 10 times greater than the tphys of the daughter. A classical example is the Mo-99/Tc-99m Generator. During the 67 hr period representing 11 half-lives of Tc-99m, 50% of the Mo-99 has disappeared, as noted in the following diagram. In both transient and secular equilibrium, apparent half-life of the daughter = physical half-life of the parent Transient Equilibrium Between elutions, the daughter (Tc-99m) builds up as the parent (Mo-99) continues to decay.
After approximately 23 hours the Tc-99m activity reaches a maximum, at which time the production rate and the decay rate are equal and the parent and daughter are said to be in transient equilibrium
Transient equilibrium occurs when the half-life of the parent is greater than that of the daughter by a factor of ~10 Secular Equilibrium
If the half-life of the parent is very much longer than that of the daughter (I.e., more than about 100 longer), secular equilibrium occurs after approximately five to six half-lives of the daughter In secular equilibrium, the activity of the parent and the daughter are the same if all of the parent atoms decay directly to the daughter Once secular equilibrium is reached, the daughter will have an apparent half-life equal to that of the parent