Synthesis of 18F
  1. USP <823> is the regulatory aspect in the radiopharmaceutical compounding of PET tracers
    1. Issue - testing for endotoxins and pathogens on radiopharmaceuticals that have very short lived agents
    2. In the future (~2011) all cyclotrons will have to have a manufacturer license
  2. Molecular imaging occurs
    1. Basic agents used in PET are elements that occur at the cellular level:  C, N, O, F
    2. Relates to the concept of molecular imaging
  3. Nucleophilic Substitution
    1. Replaces a group or element within molecule or molecular chain
    2. Radiolabeling of FDG is done in this manner

      3.  

      Nucleophilic substitution leads to hydrolysis that produces FDG

      1. Mannose Triflate (1) is the initial component needed to develop FDG
      2. Trimethly sulfate (OSO2CF3) is the leaving group within the carbon ring that is (2) replaced by 18F via nucleophilic substitution
      3. Acetal groups (H3COCO and OCOCH3) are removed and replaced with OH - hydrolysis with the end result FDG (3)
        1. Can be done by adding an acid or a base
        2. Hyrdolysis by adding HCl or NaOH
      4. Note the above reactions are color coded
      5. Once FDG has be produced
        1. Acetone and acetanitriles helps clean/remove contaminates
        2. Usually occurs in collums
        3. Micropore filter is used to assist in sterilezation and filtering of the final product 18FDG
    3. Everything is now done on a cassette that contains all the necessary compounds to label 18F
      1. Very efficient
      2. Has all the components needed to tag
      3. Hook up the lap top
      4. The process then takes about 25 minutes
      5. Other types of nucleophilic substitution can make different
        1. 18Fluorothymidine (FLT) gives a 6 - 12% yeild
        2. Cleanup becomes more difficult:  requires pressure device, seperations, and then capturing the labeled compound
        3. Cost $50k to $250k
    4. Test required on FDG prior to injection into a patient
      1. Visual - is it clear and colorless and lacks particles?
      2. Filter member integrity - air pressure test to make sure that the filter isn't broken
      3. Radiochemical purity - <4% free
      4. Radionuclidic purity - Where are the peaks 511 and 1024 keV
      5. Radionuclidic identity - measure decay to make sure that T1/2 is 109 minutes
      6. pH - must be between5.5 to 7.5
      7. Pryrogens/endotoxins - LAL
      8. Chemical purity - other purities are missing with gas and thin layer chomotography (Kryptofix 222)
        1. Different products appear at different times on the graph
        2. Radiolysis
        3. HPLC - High Pressure Liquid Chromatography
      9. Sterility - Soy broth to see what cooks (2 weeks)
      10. 2-chloro-2-Deoxy-Dglucose - you get this if in hydrolysis you add HCl instead of NaOH
    5. Must be made in a class 100 room surrounded by a class 1000 room - sterile environment

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11/20/2009