PSMA for PET Imaging of Prostate Cancer

Sollert²,

EJNMMI radiopharm. chem.

et al. 2020

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-PSMA-11 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 67Ga 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 shelf-life. 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.

Section: Introductionmentioning

confidence: 99%

“…The most recent main contributor to the expansion of 68 Ga-based PET has been imaging of the prostate specific membrane antigen (PSMA) with a host of new radiopharmaceuticals (Ruangma et al 2018 ). Of these new agents, [ 68 Ga]Ga-PSMA-11 has been most widely used to date (Hope et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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

Sollert²,

EJNMMI radiopharm. chem.

et al. 2020

“…In the United States, DOTATATE labeled with 68 Ga (NETSPOT) and 177 Lu (Lutathera) by the U.S. Food and Drug Administration for NET diagnosis and therapy while, the European Union approved [ 68 Ga]DOTATOC (SomaKIT TOC) and Lutathera. Subsequent development of theranostic agents for infection/in ammation (Velikyan 2018), prostate cancer (Eder et al 2014;Lenzo et al 2018;Ruangma et al 2018), C-X-C chemokine receptor type 4 (CXCR4) (Gourni et al 2011;Herrmann et al 2016) and, most recently, broblast activation protein inhibitors (FAPI) (Kratochwil et al 2019) is further driving demand and highlights the need for access to a reliable (and economical) supply of gallium-68 that is the focus of this paper. Analogous development of a reliable pipeline of therapeutic radionuclides is also an urgent need for the nuclear medicine community (Herrmann et al 2020), but beyond the scope of this article.…”

Section: Introductionmentioning

confidence: 99%

“…The most recent main contributor to the expansion of 68 Ga-based PET has been imaging of the prostate speci c membrane antigen (PSMA) with a host of new radiopharmaceuticals (Ruangma et al 2018). Of these new agents, [ 68 Ga]Ga-PSMA-11 has been most widely used to date (Hope et al 2017).…”

Section: Introductionmentioning

confidence: 99%

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

Sollert

et al. 2020

Preprint

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-PSMA-11 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 67Ga 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 shelf-life. 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, 45mCi) 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.

“…Over the last decade, there has also been a marked increase in the clinical use of 68 Ga that has been attributed to the ease of acquiring 68 Ga from 68 Ge/ 68 Ga generators and the development and approval of new theranostic tracers (5). The diagnostic applications of 68 Ga vary across jurisdictions/countries and include imaging of neuroendocrine tumors (1), infection/in ammation (4), prostate cancer (2,3,6), and most recently, broblast activation protein inhibitors (FAPI)(7) that was the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2019 image of the year. 68 Ga is usually produced from a 68 Ge/ 68 Ga generator, and thus can be readily implemented in PET facilities that do not have a cyclotron.…”

Section: Introductionmentioning

confidence: 99%

Cyclotron-Based Production of 68Ga, [68Ga]GaCl3, and [68Ga]Ga-PSMA-11 from a Liquid Target

Sollert

et al. 2020

Preprint

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-PSMA-11 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 67Ga 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 shelf-life. 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 (~1.67GBq, 45mCi) 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.