Dataset Information

Fully-automated production of [⁶⁸Ga]Ga-Trivehexin for clinical application and its biodistribution in healthy volunteers.

ABSTRACT:

Background

The α_vβ₆-integrin targeting trimeric ligand [⁶⁸Ga]Ga-Trivehexin has emerged as a promising candidate for clinical application due to its clinical imaging potentials in various malignant cancers. Our objective was to develop a simplified and reproducible module-based automated synthesis protocol to expand its availability in clinical application.

Methods

The pH value and the precursor load of radiolabeling were explored using an iQS-TS fully-automated module. Radiochemical purity was evaluated by radio-HPLC and radio-TLC. The ethanol content, radionuclide purity and identity, bacterial endotoxins, sterility, and stability of the final product [⁶⁸Ga]Ga-Trivehexin were all tested. Biodistribution of [⁶⁸Ga]Ga-Trivehexin in healthy volunteers was also conducted.

Results

The synthesis was explored and established using fully-automated module with outstanding radiochemical purity (>99%). Considering molar activity and economic costs, a pH of 3.6 and precursor dose of 30 μg were determined to be optimal. All relevant quality control parameters were tested and met the requirement of European Pharmacopoeia. In vitro stability test and imaging in healthy volunteer indicated the practical significance in clinical routines.

Conclusions

A fully-automated synthesis protocol for [⁶⁸Ga]Ga-Trivehexin using the iQS-TS synthesis module was achieved and conformed to the clinical quality standards.

Clinical trial registration

ClinicalTrials.gov, NCT05835570. Registered 28 April 2023, https://www.clinicaltrials.gov/study/NCT05835570.

SUBMITTER: Wang B

PROVIDER: S-EPMC11327152 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fully-automated production of [<sup>68</sup>Ga]Ga-Trivehexin for clinical application and its biodistribution in healthy volunteers.

Wang Binchen B Jiang Yaqun Y Zhu Jiaxu J Wu Huiqin H Wu Jianyuan J Li Ling L Huang Jianying J Xiao Zhiwei Z He Yong Y

Frontiers in oncology 20240802

<h4>Background</h4>The α<sub>v</sub>β<sub>6</sub>-integrin targeting trimeric ligand [<sup>68</sup>Ga]Ga-Trivehexin has emerged as a promising candidate for clinical application due to its clinical imaging potentials in various malignant cancers. Our objective was to develop a simplified and reproducible module-based automated synthesis protocol to expand its availability in clinical application.<h4>Methods</h4>The pH value and the precursor load of radiolabeling were explored using an iQS-TS fu ...[more]

PMID: 39156699

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Project description:Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in pancreatic islets, especially in β-cells, and highly expressed in human insulinomas and gastrinomas. In recent years several GLP-1R-avid radioligands have been developed to image insulin-secreting tumors or to provide a tentative quantitative in vivo biomarker of pancreatic β-cell mass. Exendin-4, a 39-amino acid peptide with high binding affinity to GLP-1R, has been labeled with Ga-68 for imaging with positron emission tomography (PET). Preparation conditions may influence the quality and in vivo behavior of tracers. Starting from a published synthesis and quality controls (QCs) procedure, we have developed and validated a new rapid and simple UV-Radio-HPLC method to test the chemical and radiochemical purity of [68Ga]Ga-NODAGA-exendin-4, to be used in the clinical routine. Methods: Ga-68 was obtained from a 68Ge/68Ga Generator (GalliaPharma®) and purified using a cationic-exchange cartridge on an automated synthesis module (Scintomics GRP®). NODAGA-exendin-4 contained in the reactor (10 µg) was reconstituted with HEPES and ascorbic acid. The reaction mixture was incubated at 100 °C. The product was purified through HLB cartridge, diluted, and sterilized. To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document released by the International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. Therefore, a range of concentrations of Ga-NODAGA-exendin-4, NODAGA-exendin-4 (5, 4, 3.125, 1.25, 1, and 0.75 μg/mL) and [68Ga]Ga-NODAGA-exendin-4 were analyzed. To validate the entire production process, three consecutive batches of [68Ga]Ga-NODAGA-exendin-4 were tested. Results: Excellent linearity was found between 5-0.75 μg/mL for both the analytes (NODAGA-exendin-4 and 68Ga-NODAGA-exendin-4), with a correlation coefficient (R2) for calibration curves equal to 0.999, average coefficients of variation (CV%) < 2% (0.45% and 0.39%) and average per cent deviation value of bias from 100%, of 0.06% and 0.04%, respectively. The calibration curve for the determination of [68Ga]Ga-NODAGA-exendin-4 was linear with a R2 of 0.993 and CV% < 2% (1.97%), in accordance to acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed using 10 μg of peptide. The mean radiochemical yield was 45 ± 2.4% in all the three validation batches of [68Ga]Ga-NODAGA-exendin-4. The radiochemical purity of [68Ga]Ga-NODAGA-exendin-4 was >95% (97.05%, 95.75% and 96.15%) in all the three batches. Conclusions: The developed UV-Radio-HPLC method to assess the radiochemical and chemical purity of [68Ga]Ga-NODAGA-exendin-4 is rapid, accurate and reproducible like its fully automated production. It allows the routine use of this PET tracer as a diagnostic tool for PET imaging of GLP-1R expression in vivo, ensuring patient safety.

Project description:PurposeThe chemokine receptor CXCR4 is overexpressed in various types of human cancers. As a specific imaging agent of CXCR4, (68)Ga-NOTA-NFB was investigated in this study to assess its safety, biodistribution and dosimetry properties in healthy volunteers, and to preliminarily evaluate its application in glioma patients.MethodsSix healthy volunteers underwent whole-body PET scans at 0, 0.5, 1, 2 and 3 h after (68)Ga-NOTA-NFB injection (mean dose, 182.4 ± 3.7 MBq (4.93 ± 0.10 mCi)). For time-activity curve calculations, 1 mL blood samples were obtained at 1, 3, 5, 10, 30, 60, 90, 120, 150 and 180 min after the injection. The estimated radiation doses were calculated by OLINDA/EXM software. Eight patients with glioma were enrolled and underwent both (68)Ga-NOTA-NFB and (18)F-FDG PET/CT scans before surgery. The expression of CXCR4 on the resected brain tumor tissues was determined by immunohistochemical staining.Results(68)Ga-NOTA-NFB was safe and well tolerated by all subjects. A rapid activity clearance from the blood circulation was observed. The organs with the highest absorbed doses were spleen (193.8 ± 32.5 μSv/MBq) and liver (119.3 ± 25.0 μSv/MBq). The mean effective dose was 25.4 ± 6.1 μSv/MBq. The maximum standardized uptake values (SUVmax) and the maximum target to non-target ratios (T/NTmax) of (68)Ga-NOTA-NFB PET/CT in glioma tissues were 4.11 ± 2.90 (range, 0.45-8.21) and 9.21 ± 8.75 (range, 3.66-24.88), respectively, while those of (18)F-FDG PET/CT were 7.34 ± 2.90 (range, 3.50-12.27) and 0.86 ± 0.41 (range, 0.35-1.59). The histopathological staining confirmed that CXCR4 was overexpressed on resected tumor tissues with prominent (68)Ga-NOTA-NFB uptake.ConclusionWith a favorable radiation dosimetry profile, (68)Ga-NOTA-NFB is safe for clinical imaging. Compared to (18)F-FDG PET/CT, (68)Ga-NOTA-NFB PET/CT is more sensitive in detecting glioma and could have potential in diagnosing and treatment planning for CXCR4 positive patients.

Dataset Information

Fully-automated production of [⁶⁸Ga]Ga-Trivehexin for clinical application and its biodistribution in healthy volunteers.

Background

Methods

Results

Conclusions

Clinical trial registration

Publications

Fully-automated production of [<sup>68</sup>Ga]Ga-Trivehexin for clinical application and its biodistribution in healthy volunteers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Fully-automated production of [68Ga]Ga-Trivehexin for clinical application and its biodistribution in healthy volunteers.

Background

Methods

Results

Conclusions

Clinical trial registration

Publications

Fully-automated production of [<sup>68</sup>Ga]Ga-Trivehexin for clinical application and its biodistribution in healthy volunteers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Fully-automated production of [⁶⁸Ga]Ga-Trivehexin for clinical application and its biodistribution in healthy volunteers.