SNMMI 2016 Oral presentation M, Otabashi; C, Desfours ; T, Vergote - - PowerPoint PPT Presentation

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SNMMI 2016 Oral presentation M, Otabashi; C, Desfours ; T, Vergote - - PowerPoint PPT Presentation

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SNMMI 2016 Oral presentation M, Otabashi; C, Desfours ; T, Vergote ; L, Brichard; JL, Morelle and G, Philippart Trasis SA, Liege, Belgium 1 Indications and Relevance of FCholine Choline is a precursor in the biosynthesis of phospholipid in

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M, Otabashi; C, Desfours ; T, Vergote ; L, Brichard; JL, Morelle and G, Philippart Trasis SA, Liege, Belgium

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SNMMI 2016 – Oral presentation

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Indications and Relevance of FCholine

Choline is a precursor in the biosynthesis of phospholipid in the cell membrane

J Nucl Med 2010; 51:1699–1706

Hepatocellular carcinoma FDG FCholine Prostate cancer recurrence

AIPES, Courtesy Dr. S. Goldman

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Classical method: Dibromomethane precursor

Nuclear Medicine and Biology 38 (2011) 1143 CANCER RESEARCH 61, 110–117, 1, 2000

Production problems:

  • Fluctuating yields
  • Generation of radioactive gas
  • Low chemical purity
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Alternative method optimized by Trasis

Nuclear Medicine and Biology 38 (2011) 637–644 Eur J Nucl Med Mol Imaging (2010) 37:2136–2145

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Alternative method optimized by Trasis

  • Stable yields (25-30% ndc) at all activity levels
  • No radioactive gas release
  • High chemical purity

AllinOne synthesizer with FCholine configuration

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Alternate method optimized by Trasis

The process and its by-products:

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Alternate method optimized by Trasis

The process and its by-products:

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Alternate method optimized by Trasis

The process and its by-products:

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Alternate method optimized by Trasis

The process and its by-products:

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Overall Layout on AllinOne

Fluoride purification and elution Labelling and alkylation

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Overall Layout on AllinOne

Purification and formulation

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Final product analysis

Compound Quantity Measurement method [18F]fluror methyl tosyl 0% TLC-HPLC [18F] Tosyl Fluoride 0% TLC-HPLC Methane ditosyl (precursor) < LOD (*) HPLC Tosyl choline < LOD (**) HPLC DMAE < 1µg/ ml HPLC Kryptofix < 20 µg/mL Spot test DMF < LOQ (***) GC MeCN < LOQ (***) GC EtOH < 500 ppm GC

(***) Limit of quantification (20 ppm) (**) Limit of detection (0,001 µmol/ml) (*) Limit of detection (0,01 µg/ml)

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FCholine: Quality Control

European pharmacopeia USP Trasis values

Radiochemical purity

≥ 90 % ≥ 90 % ≥ 97 %

Residual solvents

MeCN < 410 ppm Ethanol < 5000 ppm DMF < 880 ppm MeCN < 410 ppm Ethanol < 5000 ppm DMF < 880 ppm MeCN < LOQ (*) Ethanol < 500 ppm DMF < LOQ (*)

Chemical purity DMAE

< 10 µg/mL < 1µg/ ml

pH

4,5 -8,5 4,0 – 7,0 5 ± 0,5

K222

< 220 µg/mL < 50 µg/mL < 20 µg/mL

(*) Limit of Quantification (20 ppm)

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FCholine production Kit

Ready-to-use kit with 12 months shelf life

(*) Stability study as of today : more than 12 months

Fcholine cassette

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Performance

Cassette and reagents set up time < 1 min Synthesis time 39 min Typical production yield 25 ± 5% decay un-corrected Typical radiochemical yield 32 ± 6% decay corrected [18F]-FCH final volume 15 ± 1 mL Residual activity on cassette < 1 % initial activity Stability > 95% after 10h (volumic activity at T0: 4,5 GBq/mL)

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Performance

FCH yield vs 18F- activity (customer data)

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0 40,0 45,0 50,0 0,0 50,0 100,0 150,0 200,0 250,0 300,0 350,0 400,0

Yield ndc (%)

Activity (Gbq)

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Conclusion

A fully automated method High and reproducible yields at all activity levels Ready-to-use kit with a shelf life

  • f at least 12

months No radioactive gas release Extremely low levels of DMAE Compliant to any QC testing required

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THANK YOU