Clinically Applicable Cyclotron-Produced Gallium-68 Gives High-Yield Radiolabeling of DOTA-Based Tracers

Jussing, Emma; Milton, Stefan; Samén, Erik; Moein, Mohammad Mahdi; Bylund, Lovisa; Axelsson, Rimma; Siikanen, Jonathan; Tran, Thuy

doi:10.3390/biom11081118

Cited by 22 publications

(20 citation statements)

References 25 publications

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“…In the near future, the production of [ 68 Ga]Gallium chloride by cyclotron and a liquid target will likely improve the limited amounts of injectable radioligands by starting with activities 20-30 fold greater than those obtained with a generator [9,10]. RCY should be carefully evaluated in this new scenario.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Pros and Cons in Using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007: Production, Costs, and PET/CT Applications in Patients with Prostate Cancer

Maisto

Aurilio²,

Morisco

et al. 2022

Molecules

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The aim of this work is to compare [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 PET/CT as imaging agents in patients with prostate cancer (PCa). Comparisons were made by evaluating times and costs of the radiolabeling process, imaging features including pharmacokinetics, and impact on patient management. The analysis of advantages and drawbacks of both radioligands might help to make a better choice based on firm data. For [68Ga]Ga-PSMA-11, the radiochemical yield (RCY) using a low starting activity (L, average activity of 596.55 ± 37.97 MBq) was of 80.98 ± 0.05%, while using a high one (H, average activity of 1436.27 ± 68.68 MBq), the RCY was 71.48 ± 0.04%. Thus, increased starting activities of [68Ga]-chloride negatively influenced the RCY. A similar scenario occurred for [18F]PSMA-1007. The rate of detection of PCa lesions by Positron Emission Tomography/Computed Tomography (PET/CT) was similar for both radioligands, while their distribution in normal organs significantly differed. Furthermore, similar patterns of biodistribution were found among [18F]PSMA-1007, [68Ga]Ga-PSMA-11, and [177Lu]Lu-PSMA-617, the most used agent for RLT. Moreover, the analysis of economical aspects for each single batch of production corrected for the number of allowed PET/CT examinations suggested major advantages of [18F]PSMA-1007 compared with [68Ga]Ga-PSMA-11. Data from this study should support the proper choice in the selection of the PSMA PET radioligand to use on the basis of the cases to study.

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Section: Discussionmentioning

confidence: 99%

Analysis of Pros and Cons in Using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007: Production, Costs, and PET/CT Applications in Patients with Prostate Cancer

Maisto

Aurilio²,

Morisco

et al. 2022

Molecules

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“…Upon purification, generator eluate was loaded on a SPE column filled with 50 mg RE2 resin. The RE2 resin was then rinsed with 1 mL of 2 M HCl containing 1 mg sodium ascorbate to remove Fe(III) by reducing it to Fe(II) [ 34 ]. Then, 7.4 MBq of purified 212 Bi was eluted into the reaction vessel containing 1 or 5 µM PSC-PEG-T in 1 M NaOAc buffer at final pH 5.4.…”

Section: Methodsmentioning

confidence: 99%

Preclinical Evaluation of a Lead Specific Chelator (PSC) Conjugated to Radiopeptides for 203Pb and 212Pb-Based Theranostics

Baumhover

Liu

et al. 2023

Pharmaceutics

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203Pb and 212Pb have emerged as promising theranostic isotopes for image-guided α-particle radionuclide therapy for cancers. Here, we report a cyclen-based Pb specific chelator (PSC) that is conjugated to tyr3-octreotide via a PEG2 linker (PSC-PEG-T) targeting somatostatin receptor subtype 2 (SSTR2). PSC-PEG-T could be labeled efficiently to purified 212Pb at 25 °C and also to 212Bi at 80 °C. Efficient radiolabeling of mixed 212Pb and 212Bi in PSC-PEG-T was also observed at 80 °C. Post radiolabeling, stable Pb(II) and Bi(III) radiometal complexes in saline were observed after incubating [203Pb]Pb-PSC-PEG-T for 72 h and [212Bi]Bi-PSC-PEG-T for 5 h. Stable [212Pb]Pb-PSC-PEG-T and progeny [212Bi]Bi-PSC-PEG-T were identified after storage in saline for 24 h. In serum, stable radiometal/radiopeptide were observed after incubating [203Pb]Pb-PSC-PEG-T for 55 h and [212Pb]Pb-PSC-PEG-T for 24 h. In vivo biodistribution of [212Pb]Pb-PSC-PEG-T in tumor-free CD-1 Elite mice and athymic mice bearing AR42J xenografts revealed rapid tumor accumulation, excellent tumor retention and fast renal clearance of both 212Pb and 212Bi, with no in vivo redistribution of progeny 212Bi. Single-photon emission computed tomography (SPECT) imaging of [203Pb]Pb-PSC-PEG-T and [212Pb]Pb-PSC-PEG-T in mice also demonstrated comparable accumulation in AR42J xenografts and renal clearance, confirming the theranostic potential of the elementally identical 203Pb/212Pb radionuclide pair.

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“…Using this updated method, apparent molar activity (AMA) was determined to be in the range of 100 to 200 GBq/µmol for DOTA- based tracers. As a comparison, the clinical batches from generator 68 Ga had an AMA of 27.5–42.5 GBq/µmol for [ 68 Ga]Ga-PentixaFor (Spreckelmeyer et al 2020 ) or 13–30 GBq/µmol for [ 68 Ga]Ga-FAPI-46 (Spreckelmeyer et al 2020 ; Jussing et al 2021 ). In the case of potent ligands, the amount that can be administered without induction of pharmacological effects can be small.…”

Section: Impuritiesmentioning

confidence: 99%

Good practices for 68Ga radiopharmaceutical production

Nelson

Andersson

Wuest

et al. 2022

EJNMMI radiopharm. chem.

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Background The radiometal gallium-68 (68Ga) is increasingly used in diagnostic positron emission tomography (PET), with 68Ga-labeled radiopharmaceuticals developed as potential higher-resolution imaging alternatives to traditional 99mTc agents. In precision medicine, PET applications of 68Ga are widespread, with 68Ga radiolabeled to a variety of radiotracers that evaluate perfusion and organ function, and target specific biomarkers found on tumor lesions such as prostate-specific membrane antigen, somatostatin, fibroblast activation protein, bombesin, and melanocortin. Main body These 68Ga radiopharmaceuticals include agents such as [68Ga]Ga-macroaggregated albumin for myocardial perfusion evaluation, [68Ga]Ga-PLED for assessing renal function, [68Ga]Ga-t-butyl-HBED for assessing liver function, and [68Ga]Ga-PSMA for tumor imaging. The short half-life, favourable nuclear decay properties, ease of radiolabeling, and convenient availability through germanium-68 (68Ge) generators and cyclotron production routes strongly positions 68Ga for continued growth in clinical deployment. This progress motivates the development of a set of common guidelines and standards for the 68Ga radiopharmaceutical community, and recommendations for centers interested in establishing 68Ga radiopharmaceutical production. Conclusion This review outlines important aspects of 68Ga radiopharmacy, including 68Ga production routes using a 68Ge/68Ga generator or medical cyclotron, standardized 68Ga radiolabeling methods, quality control procedures for clinical 68Ga radiopharmaceuticals, and suggested best practices for centers with established or upcoming 68Ga radiopharmaceutical production. Finally, an outlook on 68Ga radiopharmaceuticals is presented to highlight potential challenges and opportunities facing the community.

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Clinically Applicable Cyclotron-Produced Gallium-68 Gives High-Yield Radiolabeling of DOTA-Based Tracers

Cited by 22 publications

References 25 publications

Analysis of Pros and Cons in Using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007: Production, Costs, and PET/CT Applications in Patients with Prostate Cancer

Analysis of Pros and Cons in Using [68Ga]Ga-PSMA-11 and [18F]PSMA-1007: Production, Costs, and PET/CT Applications in Patients with Prostate Cancer

Preclinical Evaluation of a Lead Specific Chelator (PSC) Conjugated to Radiopeptides for 203Pb and 212Pb-Based Theranostics

Good practices for 68Ga radiopharmaceutical production

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