Nuclear chemistry

Beam (structure)

Yield (engineering)

Metallurgy

Materials science

Chromatography

Proton

Nuclear physics

Radiochemistry

Gallium

Physics

Extraction (chemistry)

Organic chemistry

Optics

Analytical Chemistry (journal)

Chemistry

Cyclotron

EJNMMI Radiopharmacy and Chemistry

Purpose To optimize the direct production of 68 Ga on a cyclotron, via the 68 Zn(p,n) 68 Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced 68 Ga, extraction of [ 68 Ga]GaCl 3 and subsequent [ 68 Ga]Ga-PSMA-11 labeling using an automated synthesis module. Methods Irradiations of a 1.0 M solution of [ 68 Zn]Zn(NO 3 ) 2 in dilute (0.2–0.3 M) HNO 3 were conducted using GE PETtrace cyclotrons and GE 68 Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of 67 Ga through the 68 Zn(p,2n) 67 Ga reaction without unduly compromising 68 Ga yields. We also evaluated the effects of varying beam times (50–75 min) and beam currents (27–40 μA). Crude 68 Ga production was measured. The extraction of [ 68 Ga]GaCl 3 was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [ 68 Ga]GaCl 3 was used to label [ 68 Ga]Ga-PSMA-11 that was intended for clinical use. Results The decay corrected yield of 68 Ga at EOB was typically &gt; 3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [ 68 Zn]Zn(NO 3 ) 2 at 0.3 M HNO 3. Target/chemistry performance was more consistent when compared with 0.2 M HNO 3 . Radionuclidic purity of 68 Ga was typically &gt; 99.8% at EOB and met the requirements specified in the European Pharmacopoeia (&lt; 2% combined 66/67 Ga) for a practical clinical product shelf-life. The activity yield of [ 68 Ga]GaCl 3 was typically &gt; 50% (~ 1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [ 68 Ga]Ga-PSMA-11 were near quantitative (~ 1.67 GBq, 45 mCi) at EOS. Cyclotron produced [ 68 Ga]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 [ 68 Ga]Ga-PSMA-11 and is a viable alternative to traditional 68 Ge/ 68 Ga generators.

Cyclotron-based production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a liquid target