Validation of 68Ge/68Ga generator processing by chemical purification for routine clinical application of 68Ga-DOTATOC

Asti, Mattia; Pietri, G. De; Fraternali, Alessandro; Grassi, Elisa; Sghedoni, Roberto; Fioroni, Federica; Roesch, Frank; Versari, Annibale; Salvo, Diana

doi:10.1016/j.nucmedbio.2008.04.006

Cited by 97 publications

(82 citation statements)

References 11 publications

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“…However, for practical purposes 68 Ge should be kept below 0.01%, so that high volumes of long-lived liquid waste are not generated. The reported DOTA precursor labeling was also lower (60%-90% in 15 min at 95°C) than that obtained when using the TiO 2 -based IGG100 (.95% in 10-15 min at 95°C) (11).…”

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confidence: 61%

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Comprehensive Quality Control of the ITG ⁶⁸Ge/⁶⁸Ga Generator and Synthesis of ⁶⁸Ga-DOTATOC and ⁶⁸Ga-PSMA-HBED-CC for Clinical Imaging

et al. 2016

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A good-manufacturing-practices (GMP) 68 Ge/ 68 Ga generator that uses modified dodecyl-3,4,5-trihydroxybenzoate hydrophobically bound to a octadecyl silica resin (C-18) as an adsorbent has been developed that allows for dilute HCl (0.05N) to efficiently elute metal-impurity-free 68 Ga 31 ready for peptide labeling. We characterized the performance of this generator system over a year in conjunction with the production of 68 Ga-labeled DOTATOC and Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (PSMA-HBED-CC) intended for clinical studies and established protocols for batch release. Methods: A 2,040-MBq self-shielded 68 Ge/ 68 Ga generator provided metal-free 68 GaCl 3 ready for peptide labeling in the fluidic labeling module after elution with 4 mL of 0.05N HCl. The compact system was readily housed in a laminar flow cabinet allowing an ISO class-5 environment. 68 Ga labeling of peptides using GMP kits was performed in 15-20 min, and the total production time was 45-50 min. Batch release quality control specifications were established to meet investigational new drug submission and institutional review board approval standards. Results: Over a period of 12 mo, 68 Ga elution yields from the generator averaged 80% (range, 72.0%-95.1%), and 68 Ge breakthrough was less than 0.006%, initially decreasing with time to 0.001% (expressed as percentage of 68 Ge activity present in the generator at the time of elution), a unique characteristic of this generator. The radiochemical purity of both 68 Ga-DOTATOC and 68 Ga-PSMA-HBED-CC determined by highperformance liquid chromatography analysis was greater than 98%, with a minimum specific activity of 12.6 and 42 GBq/μmol, respectively. The radionuclidic ( 68 Ge) impurity was 0.00001% or less (under the detection limit). Final sterile, pyrogen-free formulation was provided in physiologic saline with 5%-7% ethanol. Conclusion: The GMP-certified 68 Ge/ 68 Ga generator system was studied for a year. The generator system is contained within the fluidic labeling module, and it is compact, self-shielded, and easy to operate using simple manual techniques. The system provides radiolabeled peptides with high (.98%) radiochemical purity and greater than 80% radiochemical yield. The 68 Ge levels in the final drug products were under the detection limits at all times. 68 Ga-DOTATOC and 68 Ga-PSMA-HBED-CC investigational radiopharmaceuticals are currently being studied clinically under investigational new drug (IND) applications submitted to the U.S. Food and Drug Administration.

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confidence: 61%

“…Similarly to the IGG100 (TiO 2 -based), the 68 Ge breakthrough and minor metallic impurities (zinc, iron, tin, titanium, copper, and aluminum) represent a potential problem because they can compete with 68 Ga during complex formation (11,12). Stability studies of this generator showed 0.003% of 68 Ge in the elution, increasing to 0.08% after 100 d (13).…”

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confidence: 99%

Comprehensive Quality Control of the ITG ⁶⁸Ge/⁶⁸Ga Generator and Synthesis of ⁶⁸Ga-DOTATOC and ⁶⁸Ga-PSMA-HBED-CC for Clinical Imaging

et al. 2016

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“…A third variation of internal radiotherapy with β − emitters involves the radiosynthesis of tumour seeking agents. For this purpose the radionuclides 89 Regarding the α-emitters, to date many preclinical and some clinical studies have been performed using 211 At (T 1/2 = 7.2 h). In fact the application of 211 At has a very long story, but it is still in the research phase.…”

Section: Radionuclides For Internal Radiotherapymentioning

confidence: 99%

“…The production of the therapeutic radionuclides 32 P and 89 Sr with high specific activity is carried out in a nuclear reactor via the 32 S(n, p) 32 P and 89 Y(n, p) 89 Sr reactions, respectively. The cross sections are rather low and therefore the yields are also low.…”

Section: Radionuclides For Internal Radiotherapymentioning

confidence: 99%

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The present and future of medical radionuclide production

Qaim

2012

Radiochimica Acta

102

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Reactor and cyclotron production of medical radionuclides / γ -ray emitters for SPECT / Positron emitters for PET / Corpuscular radiation emitters for internal radiotherapy / Low and intermediate energy nuclear reactions / Radionuclide generators / Future directionsSummary. Medical radionuclide production technology is well established. Both reactors and cyclotrons are utilized for production; the positron emitters, however, are produced exclusively using cyclotrons. A brief survey of the production methods of most commonly used diagnostic and therapeutic radionuclides is given. The emerging radionuclides are considered in more detail. They comprise novel positron emitters and therapeutic radionuclides emitting low-range electrons and α-particles. The possible alternative production routes of a few established radionuclides, like 68 Ga and 99m Tc, are discussed. The status of standardisation of production data of the commonly used as well as of some emerging radionuclides is briefly mentioned. Some notions on anticipated future trends in the production and application of radionuclides are considered.

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The Chemistry of Inorganic Nuclides (⁸⁶Y,⁶⁸Ga,⁶⁴Cu,⁸⁹Zr,¹²⁴I)

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Orvig

2014

The Chemistry of Molecular Imaging

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Validation of 68Ge/68Ga generator processing by chemical purification for routine clinical application of 68Ga-DOTATOC

Cited by 97 publications

References 11 publications

Comprehensive Quality Control of the ITG ⁶⁸Ge/⁶⁸Ga Generator and Synthesis of ⁶⁸Ga-DOTATOC and ⁶⁸Ga-PSMA-HBED-CC for Clinical Imaging

Comprehensive Quality Control of the ITG ⁶⁸Ge/⁶⁸Ga Generator and Synthesis of ⁶⁸Ga-DOTATOC and ⁶⁸Ga-PSMA-HBED-CC for Clinical Imaging

The present and future of medical radionuclide production

The Chemistry of Inorganic Nuclides (⁸⁶Y,⁶⁸Ga,⁶⁴Cu,⁸⁹Zr,¹²⁴I)

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Validation of 68Ge/68Ga generator processing by chemical purification for routine clinical application of 68Ga-DOTATOC

Cited by 97 publications

References 11 publications

Comprehensive Quality Control of the ITG 68Ge/68Ga Generator and Synthesis of 68Ga-DOTATOC and 68Ga-PSMA-HBED-CC for Clinical Imaging

Comprehensive Quality Control of the ITG 68Ge/68Ga Generator and Synthesis of 68Ga-DOTATOC and 68Ga-PSMA-HBED-CC for Clinical Imaging

The present and future of medical radionuclide production

The Chemistry of Inorganic Nuclides (86Y,68Ga,64Cu,89Zr,124I)

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Comprehensive Quality Control of the ITG ⁶⁸Ge/⁶⁸Ga Generator and Synthesis of ⁶⁸Ga-DOTATOC and ⁶⁸Ga-PSMA-HBED-CC for Clinical Imaging

Comprehensive Quality Control of the ITG ⁶⁸Ge/⁶⁸Ga Generator and Synthesis of ⁶⁸Ga-DOTATOC and ⁶⁸Ga-PSMA-HBED-CC for Clinical Imaging

The Chemistry of Inorganic Nuclides (⁸⁶Y,⁶⁸Ga,⁶⁴Cu,⁸⁹Zr,¹²⁴I)