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

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 the cell membrane Prostate cancer recurrence Hepatocellular carcinoma FCholine FDG AIPES, Courtesy Dr. S. Goldman J Nucl Med 2010; 51:1699 – 1706

Classical method: Dibromomethane precursor Production problems: - Fluctuating yields - Generation of radioactive gas - Low chemical purity Nuclear Medicine and Biology 38 (2011) 1143 CANCER RESEARCH 61, 110 – 117, 1, 2000

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

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

Alternate method optimized by Trasis The process and its by-products:

Alternate method optimized by Trasis The process and its by-products:

Alternate method optimized by Trasis The process and its by-products:

Alternate method optimized by Trasis The process and its by-products:

Overall Layout on AllinOne Fluoride purification and elution Labelling and alkylation

Overall Layout on AllinOne Purification and formulation

Final product analysis Compound Quantity Measurement method [18F]fluror methyl tosyl 0% TLC-HPLC [18F] Tosyl Fluoride 0% TLC-HPLC Methane ditosyl < LOD (*) HPLC (precursor) < LOD (**) Tosyl choline HPLC DMAE < 1µg/ ml HPLC Kryptofix < 20 µg/mL Spot test < LOQ (***) DMF GC MeCN < LOQ (***) GC < 500 ppm EtOH GC (*) Limit of detection (0,01 µg/ml) (**) Limit of detection (0,001 µmol/ml) (***) Limit of quantification (20 ppm)

FCholine: Quality Control European USP Trasis values pharmacopeia Radiochemical ≥ 90 % ≥ 90 % ≥ 97 % purity Residual solvents MeCN < 410 ppm MeCN < 410 ppm MeCN < LOQ (*) Ethanol < 5000 ppm Ethanol < 5000 Ethanol < 500 ppm DMF < 880 ppm ppm DMF < LOQ (*) DMF < 880 ppm Chemical purity < 10 µg/mL < 1µg/ ml DMAE 4,5 -8,5 4,0 – 7,0 pH 5 ± 0,5 K222 < 220 µg/mL < 50 µg/mL < 20 µg/mL (*) Limit of Quantification (20 ppm)

FCholine production Kit Ready-to-use kit with 12 months shelf life Fcholine cassette (*) Stability study as of today : more than 12 months

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

Performance FCH yield vs 18F - activity (customer data) 50,0 45,0 40,0 35,0 Yield ndc (%) 30,0 25,0 20,0 15,0 10,0 5,0 0,0 0,0 50,0 100,0 150,0 200,0 250,0 300,0 350,0 400,0 Activity (Gbq)

Conclusion High and Ready-to-use kit A fully reproducible with a shelf life automated yields at all of at least 12 method activity levels months Compliant to No radioactive Extremely low any QC testing gas release levels of DMAE required

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