Cyclotron-based production of 68 Ga, [ 68 Ga]GaCl 3 , and [ 68 Ga]Ga-PSMA-11 from a liquid target

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(2020) 5:25

EJNMMI Radiopharmacy and Chemistry

RESEARCH ARTICLE

Open Access

Cyclotron-based production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a liquid target Melissa E. Rodnick1, Carina Sollert2, Daniela Stark3, Mara Clark1, Andrew Katsifis3, Brian G. Hockley1, D. Christian Parr2, Jens Frigell2, Bradford D. Henderson1, Monica Abghari-Gerst1, Morand R. Piert1, Michael J. Fulham4, Stefan Eberl5*, Katherine Gagnon2* and Peter J. H. Scott1* * Correspondence: stefan.eberl@ sydney.edu.au; katherine.gagnon@ ge.com; [email protected] 5 Department of Molecular Imaging, Royal Prince Alfred Hospital and School of Computer Science, The University of Sydney, Sydney, Australia 2 GE Healthcare, GEMS PET Systems, Uppsala, Sweden 1 Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, MI, USA Full list of author information is available at the end of the article

Abstract Purpose: To optimize the direct production of 68Ga on a cyclotron, via the 68Zn(p, n)68Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced 68Ga, extraction of [68Ga]GaCl3 and subsequent [68Ga]Ga-PSMA11 labeling using an automated synthesis module. Methods: Irradiations of a 1.0 M solution of [68Zn]Zn(NO3)2 in dilute (0.2–0.3 M) HNO3 were conducted using GE PETtrace cyclotrons and GE 68Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of 67 Ga through the 68Zn(p,2n)67Ga reaction without unduly compromising 68Ga yields. We also evaluated the effects of varying beam times (50–75 min) and beam currents (27–40 μA). Crude 68Ga production was measured. The extraction of [68Ga]GaCl3 was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [68Ga]GaCl3 was used to label [68Ga]Ga-PSMA-11 that was intended for clinical use. Results: The decay corrected yield of 68Ga at EOB was typically > 3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [68Zn]Zn(NO3)2 at 0.3 M HNO3. Target/chemistry performance was more consistent when compared with 0.2 M HNO3. Radionuclidic purity of 68Ga was typically > 99.8% at EOB and met the requirements specified in the European Pharmacopoeia (< 2% combined 66/67Ga) for a practical clinical product shelflife. The activity yield of [68Ga]GaCl3 was typically > 50% (~ 1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [68Ga]Ga-PSMA-11 were near quantitative (~ 1.67 GBq, 45 mCi) at EOS. Cyclotron produced [68Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing, and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA). Conclusion: Direct cyclotron irradiation of a liquid target provides clinically relevant quantities of [68Ga]Ga-PSMA-11 and is a viable alternative to traditional 68Ge/68Ga generators. Keywords: Gallium-68, Cyclotron targetry, Positron emission tomography, PSMA

© The Author(s). 2020 Op

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