Cyclotron production of 68Ga in a liquid target: Effects of solution composition and irradiation parameters

Pandey, Mukesh K.; Byrne, John F.; Schlasner, Katherine N.; Schmit, Nicholas R.; DeGrado, Timothy R.

doi:10.1016/j.nucmedbio.2019.03.002

Cited by 43 publications

(60 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…a few patient doses), a generator is much less technically demanding, very reliable and does not require trained personnel to perform separation and radiolabelling on synthesis modules or major capital investment in a cyclotron facility. Liquid cyclotron targets where acidic solutions containing zinc-68 salts are bombarded with protons, provide an alternative solution to get a small number of patient doses but the reported production yields of <10 GBq at EOB or approximately 5 GBq at EOP are inferior to the solid target route (8)(9)(10). This method also carries the inherent risk of acids damaging targets and potentially cyclotron systems and require continuous target maintenance.…”

Section: Discussionmentioning

confidence: 99%

Multi-Curie Production of Gallium-68 on a Biomedical Cyclotron and Automated Radiolabelling of PSMA-11 and DOTATATE

Thisgaard

Kumlin

Langkjær

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: With increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([68Ge]Ge/[68Ga]Ga) generators are incapable of supplying sufficient amounts of the short-lived daughter isotope. In this study, we demonstrate a high-yield, automated method for producing multi-Curie levels of [68Ga]GaCl3 from solid zinc-68 targets and subsequent labelling to produce clinical-grade [68Ga]Ga-PSMA-11 and [68Ga]Ga-DOTATATE.Results: Enriched zinc-68 targets were irradiated at up to 80 µA with 13 MeV protons for 120 min; repeatedly producing up to 194 GBq (5.24 Ci) of purified gallium-68 in the form of [68Ga]GaCl3 at the end of purification (EOP) from an expected >370 GBq (>10 Ci) at end of bombardment. A fully automated dissolution/separation process was completed in 35 min. Isolated product was analysed according to the draft Ph. Eur. monograph for accelerator produced [68Ga]GaCl3 and found to comply with all specifications. In every instance, the radiochemical purity exceeded 99.9% and importantly, the radionuclidic purity was sufficient to allow for a shelf-life of up to 7 h based on this metric alone. Fully automated production of up to 72.2 GBq [68Ga]Ga-PSMA-11 was performed, providing a product with high radiochemical purity (>98.2%) and very high apparent molar activities of up to 722 MBq/nmol. Further, manual radiolabelling of up to 3.2 GBq DOTATATE was performed in high yields (>95%) and with apparent molar activities (9-25 MBq/nmol) sufficient for clinical use.Conclusions: We have developed a high-yielding, automated method for the production of very high amounts of [68Ga]GaCl3, sufficient for supply proximal radiopharmacies. The reported method led to record-high purified gallium-68 activities (194 GBq at end of purification) and subsequent labelling of PSMA-11 and DOTATATE. The process was highly automated from irradiation through to formulation of the product, and as such comprised a high level of radiation protection. The quality control results obtained for both [68Ga]GaCl3 for radiolabelling and [68Ga]Ga-PSMA-11 are promising for clinical use.

show abstract

Section: Discussionmentioning

confidence: 99%

Multi-Curie Production of Gallium-68 on a Biomedical Cyclotron and Automated Radiolabelling of PSMA-11 and DOTATATE

Thisgaard

Kumlin

Langkjær

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The quantity of zinc necessary for the target need to be removed as it and all other metal impurities may perturb the radiolabeling reaction of gallium-68. Intense research on this topic lead to several purification methods based on solvent extraction [34,35], precipitation [36] and solid phase separation [37][38][39][40][41][42][43][44] and suitable for automation.…”

Section: Work In Progress: Cyclotronmentioning

confidence: 99%

Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging - A Lot to Consider

Meisenheimer¹,

Saenko²,

Eppard³

2021

Medical Isotopes

View full text Add to dashboard Cite

Gallium-68 was applied for positron emission tomography (PET) imaging already in the early beginnings of PET imaging. Today, with the introduction of PSMA-targeting tracers (e.g. PSMA-11, PSMA-617, and PSMA-I&T), the number of clinical applications of 68 Ga-radiopharmaceuticals for diagnostic imaging has grown considerably. This development was initiated and supported already in the mid-2000s by the commercial availability of 68 Ge/ 68 Ga generators designed for clinical usage. This progression was accompanied by the development of several purification methods to generator eluate as well as sophisticated 68 Ga-radiopharmaceuticals. Due to the 68 Ga-rush, the need for implementation of gallium-68 (depending on production route) and its certain tracers into the pharmacopeia increased. Based on the specifications given by the pharmacopeia, interest focused on the development of automated synthesis systems, 99m Tc-analog kits with regard to patient as well as operator safety.

show abstract

“…Gallium-68 can be produced from a long-lived 68 Ge/ 68 Ga generator, even at PET centers without its own cyclotron. In addition, 68 Ga can be produced by cyclotrons using easy-to-operate liquid targets [79].…”

Section: Labeling Of Affibody Molecules With Positron-emitting Radionmentioning

confidence: 99%

Affibody Molecules as Targeting Vectors for PET Imaging

Tolmachev

Orlova

2020

Cancers

View full text Add to dashboard Cite

Affibody molecules are small (58 amino acids) engineered scaffold proteins that can be selected to bind to a large variety of proteins with a high affinity. Their small size and high affinity make them attractive as targeting vectors for molecular imaging. High-affinity affibody binders have been selected for several cancer-associated molecular targets. Preclinical studies have shown that radiolabeled affibody molecules can provide highly specific and sensitive imaging on the day of injection; however, for a few targets, imaging on the next day further increased the imaging sensitivity. A phase I/II clinical trial showed that 68Ga-labeled affibody molecules permit an accurate and specific measurement of HER2 expression in breast cancer metastases. This paper provides an overview of the factors influencing the biodistribution and targeting properties of affibody molecules and the chemistry of their labeling using positron emitters.

show abstract

Cyclotron production of 68Ga in a liquid target: Effects of solution composition and irradiation parameters

Cited by 43 publications

References 7 publications

Multi-Curie Production of Gallium-68 on a Biomedical Cyclotron and Automated Radiolabelling of PSMA-11 and DOTATATE

Multi-Curie Production of Gallium-68 on a Biomedical Cyclotron and Automated Radiolabelling of PSMA-11 and DOTATATE

Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging - A Lot to Consider

Affibody Molecules as Targeting Vectors for PET Imaging

Contact Info

Product

Resources

About