1. Neutron rich radionuclides decay via positron by converting a P⁺ to a N^o and then release a β⁺. It also appears that there is some electron capture occurring, where the P⁺ captures an inner shell electron, converts to a N^o, then releases K-characteristics x-rays. When this happens no β⁺ is produced. Here are some of the percentages of electron capture
   1. ¹⁸F = 3.14% link
   2. ¹¹C = 0.25% link
   3. ¹³N ~13.2% link
   4. ¹⁵O = 0.115% link
2. Regulatory agencies NRC and FDA
   1. NRC use to only regulate by-product materials, but since 9/11 that philosophy has changed
      1. NUREG-1556 - Program - "Specific Guidance About Possession Licenses for Production of Radioactive Material Using an Accelerator.” published October 2007
         1. Volume 21 - "Program-Specific Eventually all State in the US will be required to regulate all radioactive materials." published October 2007
         2. Volume 13 Rev. 1 - "Program-Specific Guidance About Commercial Radiopharmacy Licenses” was published November 2007.
         3. Volume 9 Rev. 2 - “Program-Specific Guidance About Medical Use Licenses” published January 2008
   2. FDG
      1. PET producers must meet Current Good Manufacturing Practice (CGMP) that complies with CFR 212
      2. PET producers must submit a new drug application (NDA) or abbreviated new drug application (ANDA)
      3. Drug Master File (DMF) - gives detailed information about radiopharmaceutical preparation, packaging, and what the FDG likes
         1. Example FDG
   3. United States Pharmacopoeia (USP)
      1. Lecture on regulatory issues - compounding of PET radiopharmaceuticals - USP General Cahpter <823>
      2. Production
      3. QC
3. Typical positrons used in PET
   1. Most common radiopharmaceutical and positron is ¹⁸F-Fludeoxyglucose or 2-dexoxy-[¹⁸F]fluoro-D-glucose
   2. Others
      1. ¹¹C - 20.3 minutes
      2. ¹³N - 10 minutes ¹³NH₃ (ammonia)
      3. ¹⁵O - 2 minutes
      4. ¹⁸F - 109.75 minutes

4. Generator produced positrons
   1. ⁸²Rb Generator (need to do breakthrough of ⁸²Sr)
   2. ⁶²Cu Generator still under clinical investigation
5. Current market cyclotrons for PET are classified as "Negative Ion"
   
   1. How do we accelerate negative ions? 
      1. Take Hydrogen and add an e^- to its orbit (1P:2e^-). This makes it negative
      2. Or a deuteron is produced which contains 1P/1N:2e^-
   2. Cyclotrons are manufactured to produce different energy levels
      1. Lowever energy cyclotrons start off at 8 MeV
      2. Most commercial systems for PET are between 12 - 18 MeV
      3. Some are as high as 30 MeV which is required to produce ¹²⁴I
   3. FYI - As a general rule linear accelerators usually do not have enough energy to create the β⁺ needed in PET
   4. The making of FDG
      1. First you need to ¹⁸O
      2. ¹⁸O water is the target, but only 1% is found in our drinking water
      3. It can be refined to 97% which is required if you want to production of ¹⁸F
      4. Another method to producing ¹⁸F is to place ¹⁴Ne high pressure and then bombard it deuteron
   5. Beam production and the operation of a cyclotron (use mouse over to see the beam - this may not work in Bb, see other site)
   
   1. Ion Source is the where the negatively charged ions enter the system
   2. As they spins out outward the energy of the negative ions increases
   3. Speed increases with the enhancement of the four Dees, which alternate a charge (polarity) where each dee causing the ion particle to increase its speed in a controlled path which is contained by a magnetic field
   4. This polarity causes the ion to either be attracted or repelled along its path pending its location (as it crosses from one Dee to the other)
   5. Dee's change polarity ~ 3.0 x 10⁶/second
   6. The orbit is not really circular, but angled with the shape of the Dee, as the atom pushed/pulled along with variation in charge
   7. The beam is 6-8 mm beam in diameter, focused, as it increases in energy as it goes "up hill" and coasts in the the valley (look at the Dee structure)
   8. After ~200 cycles, the atom is at the edge of the Dees where it fly off the Dee and head for for a target (note - there are multiple takes which allows you to make more than "batch" at a time of the same product or another product)
   9. Prior to reaching the target it strikes an extraction foil
      1. This carbon foil is only a few atoms thick
      2. It strips off the electrons leaving just the proton. The proton continues to the target
      3. Note - electrons and protons spin in different directions and when the electrons are stripped off the beam the negatively charged ion becomes positive
      4. Placement of the foil can vary with one or more targets being bombarded
   10. An advantage of a negative ion cyclotron is that does not become radioactive or contaminated therefore making it easier to decommission
   
   
   6. Target for producing ¹⁸F
      1. The proton beam then head to its target
      2. In front of the target is Helium that is under pressure with a thin foil covering the gas
      3. Foils are referred to as Haver foils
      4. On the opposite side of ¹⁸O is water under pressure acting as a coolant
      5. In the center is the ¹⁸O being bombarded with protons
      6. Adding protons to the mix produces ¹⁸F - ¹⁸O (p,n)¹⁸F
      7. Every two to three hours ¹⁸F can be extracted, more ¹⁸O can be added and the process continues
      8. Usually several thousand mCi's are produced
      9. Question - If 15mCi of ¹⁸F is calibrated for 10am, how many mCi are there if the dose was extracted from the cyclotron at 4am?
         1. If 6 hours has transpired then
         2. Answer

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How is FDG made?

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