Baguet, Tristan

De Lombaerde, Stef

De Vos, Filip

Descamps, Benedicte

Goethals, Ingeborg

Vanhove, Christian

Verhoeven, Jeroen

Ghent University Academic Bibliography

• Radiosynthesis: Optimization 18F labelling• Solvent • Temperature• Mass of the precursor• In vivo testing• PC-3 xenograft (5 x 106 cells) (n=2). • Radiosynthesis 20 minutes in acetonitrile at 120°C. • Followed by deprotection with HCl (4M/dioxane) 5 minutes at 90°C.• Purification was done by means of semi-prep HPLC.• Final formulation: 20% EtOH/80% PBS mixture. • Dynamic µPET-scan acquired for 2 hours after injection of 18.5 MBq. • Volumes of interest are drawn around the tumor and the contralateral side as reference region with PMOD. MATERIALS & METHODS020406080DMSO DMF ACNLabelling yield (%)SolventLabelling yield in fuction of solvent0204060801000 2 4 6 8 10Labelling yield (%)Mass precursor (mg)Labelling yield in function of mass precursorRESULTSCONCLUSIONSCONTACT: Tristan.baguet@ugent.beCancer is characterized by upregulation of nutrient transporters such as GLUT-1, LAT-1 and ASCT-2. [18F] FDG is the golden standard in oncology metabolism imaging, however this tracer shows sub-optimal characteristics in several tumors (e.g. brain-, prostate-, colorectal cancer). In a search to address these drawbacks, a 18F labeled inhibitor ([18F] (S)-2-amino-4-((2-((3-fluorobenzyl)oxy)benzyl)(2-((3-(fluoromethyl)benzyl)oxy)benzyl)amino)butanoic acid) of ASCT-2 was developed. INTRODUCTIONWith this study we report a new radiolabeled inhibitor of ASCT-2, which shows a good TBR. Further experiments are needed to explore the imaging potential of the ASCT-2 transporter. Optimal labelling conditions are also reported which suggest the labelling should occur in acetonitrile with a temperature of 120°C. Tristan Baguet1, S. De Lombaerde1,J. Verhoeven1, B. Descamps2, I. Goethals3C. Vanhove2, F. De Vos11Ghent University, Laboratory for Radiopharmacy2Ghent University, IBiTech-MEDISIP-INFINITY3Ghent University, Nuclear medicineGhent, BelgiumRadiosynthesis and in vivo evaluation of [18F] FABABA, a new ASCT-2 inhibitor.Figure 1: Labelling yield in function of different solvents. Altering the solvent to acetonitrileresulted in substantial increase in labelling yield.02040608010050 60 70 80 90 100 110 120 130Labelling yield (%)Temperature (°C)Labelling yield in fuction of temperature Figure 2: In the temperature-yield curve an inflection point is seen between 100°C and 120°C, suggesting this accounts for the Ekin necessary for good labelling yields. Figure 3: Labelling yield in function of the mass shows increase in yield at 2mg.  Increasing the amount of precursor further from 2mg to 8mg did not increase the labelling yield significantly. Figure 4: µPET/CT image of PC-3 xenograft.The tracer shows in vivo uptake in the tumor and makes a clear delineation of the tumor possible. Furthermore it is predominantly cleared via biliary transport and in a minor amount to the bladder. The tracer reports an optimal uptake in the tumor after 20 minutes and an average tumor to background ratio of 1.85 ± 0,13 (n=2). 

Radiosynthesis and in vivo evaluation of [18F] FABABA, a new ASCT-2 inhibitor

https://biblio.ugent.be/publication/8573380/file/8573385

Radiosynthesis and in vivo evaluation of [18F] FABABA, a new ASCT-2 inhibitor

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Ghent University Academic Bibliography