Automated synthesis and quality control of [68Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging

doi:10.21203/rs.3.rs-2364212/v1

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Research Article

Automated synthesis and quality control of [68Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging

https://doi.org/10.21203/rs.3.rs-2364212/v1

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published 07 Feb, 2023

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Background

[⁶⁸Ga]Ga-PentixaFor is a promising radiotracer for positron emission tomography imaging of several human tumors overexpressing the chemokine receptor-4 (CXCR4). CXCR4 overexpression has been demonstrated in patients with hematologic malignancies, solid cancers, as well as cardiovascular pathologies of inflammatory origins. However, its radio synthesis is not yet fully developed in France, and existing methods do not use our type of synthesis module. Therefore, we aimed at developing a [⁶⁸Ga]Ga-PentixaFor synthesis with Gaia/Luna Elysia-Raytest module to use it in clinical purpose.

Results

12 syntheses were carried out by varying the temperature conditions and radiolabeling times, and led to choose specific labelling conditions with the Gaia/Luna Elysia-Raytest module: 97°Celsius, 4 minutes. The mean 3 Good Manufacturing Practice (GMP)-conditions synthesis time was 24 min 27 s (+/- 8 s), and the mean radiolabeling efficiency was 86.96% (Standard deviation (SD) 6.67%). Different quality control parameters were also evaluated in accordance with European Pharmacopeia: radiochemical and radionuclidic purity, pH, sterility, stability and endotoxins levels. The average radiochemical purity was 99.09% (SD 0.25%) assessed by Instant Thin Layer Chromatography and 99.82% (SD 0.092%) assessed by High Pressure Liquid Chromatography. Average 68-germanium breakthrough was 0.0000148%, under the recommended level of 0.001%. We assessed the stability of the radiotracer up to 4 hours at room temperature (no augmentation of the ^[68Ga] chloride in the final product, i.e. radiochemical purity (RCP) > 98.5%). The endotoxins levels were < 5.00 EU/mL, and the pH was 6.5 (same for the three syntheses).

Conclusion

The [⁶⁸Ga]Ga-PentixaFor synthesis process developed on the Gaia/Luna Elysia-Raytest module has fulfilled all acceptance criteria for injectable radiopharmaceutical products regarding the European Pharmacopeia. The radiochemical purity, stability, efficacy, as well as the microbiological quality of the three GMP batches were found to be good. The robustness of the synthesis process may be suitable for multi-dose application in clinical settings.

PET

PentixaFor

CXCR4

68Ga

automated synthesis

radiopharmacy

The transmembrane chemokine receptor-4 (CXCR4) is involved in in embryogenesis, neoangiogenesis, hematopoiesis, and inflammation physiological process throw the CXCR4/CXCL12 axis (1–3). Nevertheless, its overexpression has been found to play a critical role in promoting tumor growth and progression, tumor invasiveness, and metastasis process (4). Pathologies that can be found are mainly lymphoproliferative diseases such as B-cell lymphoma and lymphocytic leukemia, as well as cardiovascular pathologies of inflammatory origins (5–7). In solid cancers the expression is more heterogeneous but is present in adrenal tumors, mammary cancer, prostate cancer or melanoma. In order to allow the evaluation and the follow-up of these pathologies, a radiotracer marking the CXCR4 receptor was developed for PET imaging (8).

[⁶⁸Ga]Ga-PentixaFor (also known as C₆₀H₇₇GaN₁₄O₁₄ or ⁶⁸Ga-CPCR4.2, Fig. 1 below) is thus a cyclic pentapeptide with high affinity to CXCR4, with suitable pharmacologic and pharmacodynamics characteristics, that make it an excellent PET imaging tracer (8–10). Its radiochemical synthesis has been developed and optimized to allow its use in clinical settings with different automated modules (11–13).

However, there is no description of a [⁶⁸Ga]Ga-PentixaFor synthesis using the Gaia/Luna Elysia-Raytest module. Nevertheless, the type of module is important as it may affect the synthesis settings, such as the rise in temperature and the heating maintenance, or the synthesis duration. We thus decided to investigate and develop the radio synthesis of [⁶⁸Ga]Ga-PentixaFor with the Gaia/Luna Elysia-Raytest module. First, we aimed at establishing the best conditions and synthesis sequences by testing a range of parameters and varying the commands of the module. Then, we aimed at carrying out GMP-grade syntheses, and performing pharmaceutical quality controls to validate the compatibility with the European Pharmacopeia. As there is no monography for [⁶⁸Ga]Ga-PentixaFor in European pharmacopeia, we took as reference the monography of [⁶⁸Ga]Ga-PSMA to validate our synthesis.

Reagents and devices

Good Manufacturing Process (GMP) grade PentixaFor and [⁶⁹Ga]Ga-PentixaFor acetate were gracefully obtained from PentixaPharm GmbH (Würzburg, Germany).

The fluidic cassette for ⁶⁸Ga labeling (sterile and single-use) and the reagents kit (including SCX and C18 cartridges, acetate buffer and HCl eluent solution, isotonic saline 0.9% solution, ethanol 60% and absolute ethanol solutions, water for injections, 0.22 µm filter and final vial – GMP grade) were purchased from ABX pharmaceuticals (Advanced Biochemical Compounds, Radeberg, Germany).

Gallium-68 was obtained by elution of a commercialized ⁶⁸Ge/⁶⁸Ga generator (GalliaPharm® 1850 MBq, Eckert & Ziegler radiopharma GmbH, Berlin, Germany) with a 0.1M HCl solution (Eckert & Ziegler). The automated radio synthesis of [⁶⁸Ga]Ga-PentixaFor was conducted on the commercial labeling synthesis module Gaia/Luna (Elysia-Raytest, GmbH, Straubenhardt, Germany). A computerized program was controlling the module, including the valves and syringes on the cassette, in order to produce the desired radiopharmaceutical.

Description of the manufacturing process

Fifty micrograms of lyophilized precursor (PentixaFor) were dissolved with 2.2 mL of acetate buffer in a syringe, which was connected to the labeling cassette. The SCX and C18 cartridges were pre conditioned before elution with Water For injections (WFI), preceded for the C18 column by 5 mL of absolute ethanol, and dried. The peptide was then transferred into the reaction flask.

The elution of the generator was then carried out with 5 mL of 0.1 molar hydrochloric acid, and the ⁶⁸Ga³⁺ was captured on the cation exchange cartridge (SCX) in order to concentrate the radioactivity, evacuating the HCl 0.1 M in waste. The SCX column was then eluted with 0.5 +/- 0.1 mL of eluent (WFI/NaCl 0.9%/HCl 32–35% mixture) directly in the reaction flask, with the peptide. This solution was heated at 97° Celsius during 4 min. The labeling was carried out at pH = 3.5.

At the end of the heating, the reaction mixture was injected into the C18, which retained the active substance ([⁶⁸Ga]Ga-PentixaFor) as well as the colloidal forms (a radiochemical impurity that can occur during ⁶⁸Ga labelling (14, 15)), and evacuated the rest of the reaction mixture as waste (with the free gallium). The reaction flask was rinsed with WFI, and this solution was also injected into the C18 column. The C18 column was then alternatively eluted with a mixture of 8.6 +/- 0.3 mL of isotonic saline solution and 1.5 mL +/- 0.1 mL of 60% ethanol, in order to elute the [⁶⁸Ga]Ga-PentixaFor, the colloidal forms remaining retained on the column. The solution was finally injected into the final vial through a 0.22 µm sterilizing filter (Millex-GV, 0.22 µm, hydrophilic, PVDF, 13 mm, sterilized with ethylene oxide) to obtain a volume of 10.1 mL +/- 0.4 mL final solution (see Fig. 2).

Radiolabeling efficiency

The labelling efficiency was determinated using the formula below (decay corrected):

$$Efficiency= \frac{C18 activity-C18 Post Elution activity }{Initial activity measured in reactor} \times 100$$

C18, C18 post elution and initial reactor activities were automatically measured and saved in the final software reports.

Optimization of the synthesis settings

First tests were carried out to establish the command sequences of the synthesis module and find interesting ranges of temperatures and heating duration to investigate. Then, these different temperatures and heating times were tested in order to determine the optimal parameters for carrying out the radiolabeling, and to ensure the robustness of the process. A fixed quantity of precursor was used (50 µg). The ranges of settings tested were 95–98°Celsius and 4-6min heating time, in agreement with the elements supplied by the PentixaPharm laboratory, the literature (11, 13, 16) and our pre-tests, leading to the evaluation of 12 synthesis conditions.

For each setting, at least one synthesis was conducted and both labeling efficiency and radiochemical purity were determined. If several syntheses were carried out, averages of the efficiencies and of the radiochemical purities were used.

Validation and process controls of GMP-quality batches

We carried out several quality controls in order to check the accordance of the final product with the requirements for quality controls of radiopharmaceuticals (European Pharmacopeia).

Appearance and pH

We conducted a visual examination of each final product to verify the clearness and color of the solution: it had to be clear and colorless to comply the test. The pH-value of the solution was determined using pH strips. The expected pH was 5.0–8.0.

Chemical identity

We developed and validated a High-Pressure Liquid Chromatography (HPLC, Shimadzu, Kyoto, Japan) method in accordance with ICH Q2 standards. Briefly, we filled out a vial with a sample of the final product. An injection of 20 µL was done in a mobile phase in gradient mode (see Table 1 below), with a fixed flow rate of 1.0 mL/min during 15 min in a Phenomenex Gemini 3m peptide NX-C188 110A LC 150 x 4.6 column (Torrance, USA). UV detection was performed at 220 nm with Diode Array Detector, and gamma detection was carried out with GABI Nova® radio flow monitor (NAI-Photomultiplier tube, Elysia-Raytest GmbH).

Table 1

Flow gradient used to perform HPLC analysis
HPLC analysis (flow = 1 mL/min)
Time (min)	Mobile phase A (%) Water/TFA 1000/1 v/v	Mobile phase B (%) Acetonitrile/TFA 1000/1 v/v
0	80	20
9	50	50
10	50	50
15	80	20

Retention time of the final solution had to comply with reference material, constituted by the non-radioactive precursor ([⁶⁹Ga]Ga-PentixaFor acetate). The retention time of [⁶⁸Ga]Ga-PentixaFor solution had to be between 90 and 110% of that of [⁶⁹Ga]Ga-PentixaFor acetate, taking into account that the UV and the gamma detectors were connected in series, so there was a fixed differential time of 15 seconds between the two analysis devices.

Radionuclear identity

A gamma-spectrometry analysis was carried out on each batch with multi-channel-analyzer for gamma-spectroscopy MUCHA® (Elysia-Raytest GmbH) to measure the energy emitted. As ⁶⁸Ga was the radionuclide of interest, we searched for the 511 keV (+/- 10%) main peak. Half-life was determined by automatized measuring of the final solution each seconds during 20 minutes. Result should be between 62 and 74 minutes (expected value of 67.71 min).

Radiochemical purity

Each batch of in-house prepared [⁶⁸Ga]Ga-PentixaFor was tested to determine the RCP of the product, and part of impurities (free ⁶⁸Ga and colloidal forms) due to the synthesis process.

We used an Instant Thin Layer Chromatography (ITLC) analysis to determine the part of free ⁶⁸Ga and colloidal forms in the sample, using a sample taken directly from the final product, with two methods:

A first migration with a mobile phase constituted with 1 mol/L ammonium acetate/methanol (1:1) and as solid phase an ITLC-SG strip (Varian iTLC-SG plates): Ga-68 colloidal forms were found with Rf = 0.0-0.2, and [⁶⁸Ga]Ga-PentixaFor with free ⁶⁸Ga at Rf = 0.8-1
A second migration with a mobile phase constituted with citrate buffer (pH = 5.0) and as solid phase an ITLC-SG strip: [⁶⁸Ga]Ga-PentixaFor was found with Rf = 0.0-0.2, and free ⁶⁸Ga and Ga-68 colloidal forms at Rf = 0.8-1

A miniGITA® TLC scanning device (Elysia-Raytest GmbH) was used to achieve the ITLC analysis.

According to the European Pharmacopoeia, it is necessary to assess the radiochemical purity using HPLC. The method described in the chemical identity paragraph (Table 1) therefore allowed us to calculate the RCP by separating the [⁶⁸Ga]Ga-PentixaFor from the free gallium (⁶⁸Ga³⁺).

Radionucleidic purity

The 68-germanium breakthrough was determined for each batch using multi-channel-analyzer for gamma-spectroscopy MUCHA® (Elysia-Raytest GmbH). 48h after the synthesis (when all the presence of ⁶⁸Ga is only due to the initial presence of ⁶⁸Ge, as the half-life of ⁶⁸Ga is 67.71 min), we measured the 511 keV peak emission due to the nuclear transformation of the 68-germanium into 68-gallium in a sample. Initial percentage of activity due to 68-germanium was calculated as below:

$$68\text{G}\text{e} \text{b}\text{r}\text{e}\text{a}\text{k}\text{t}\text{h}\text{r}\text{o}\text{u}\text{g}\text{h}= \frac{Activity 48h after synthesis \left(decay corrected\right) }{Activity measured in final vial just after synthesis} \times 100$$

Bacterial endotoxins

A LAL-test using Endosafe® (Charles River, Wilmington, USA) device was conducted on each production, diluted to 1/100 with WFI endotoxin-free. This dilution level was chosen after determination of the maximal dilution, in order to avoid product interference with the test. The test was considered valid if the samples contained less than 15 EU/mL, in accordance with European Pharmacopeia requirements.

Radiochemical stability

In order to assess the stability of the preparations, we carried out a measurement of the RCP each hour during four hours after the syntheses, which may allow us to prepare the syringe for patients in clinical use regarding the half-life of ⁶⁸Ga. The measurement were conducted using both iTLC and HPLC methods for RCP determination as previously specified.

Final composition

At the end of the synthesis, the final vial contained an average of 613.7 MBq (SD 41.19 MBq) of [⁶⁸Ga]Ga-PentixaFor, and so a specific activity of 12.27 MBq/µg (SD 0.82). The final volume of the preparation was 10.1 mL +/- 0.4 mL. It contained 0.9 mL +/- 0.06 mL of ethanol, 0.6 mL +/- 0.04 mL of WFI and 8.6 mL +/- 0.3 mL of sodium chloride, in accordance with the European Pharmacopeia requirements.

Optimization of synthesis settings

The results of the syntheses conducted with different couple of settings are presented below in Table 2.

Table 2

Radiochemical purity and labeling efficacy obtained with different synthesis settings
Temperature	Heating time	RCP	Labeling efficacy
95°C	4	93,95%	85,90%
	5	94,70%	87,72%
	6	97,12%	76,2%
96°C	4	93,77%	76,61%
	5	97,29%	88,21%
	6	95,76%	85,58%
97°C	4	98,39%	90,14%
	5	97,14%	83,22%
	6	96,00%	77,35%
98°C	4	97,59%	96,32%
	5	94,06%	79,30%
	6	94,63%	90,45%

Following these tests, we decided to carry out the GMP-grade syntheses at 97°C for 4 min.

Validation and quality control of GMP-quality batches

Three batches of [⁶⁸Ga]Ga-PentixaFor (GMP grade) were produced, using the pre-determined parameters of synthesis (97°C, 4 min). Complete synthesis reports can be found in Supplementary files 1–3. Quality controls specifications and results are presented in Table 3:

Table 3

Results of GMP syntheses with regard to the specifications of the European Pharmacopeia
Tests	Methods	Specifications	Batch 1	Batch 2	Batch 3
Characters	Visual	Clear, colorless solution	Complies	Complies	Complies
Identification: - Photons γ emission peak - period	γ-Spectrometry (Ph. Eur. 2.2.66) Ionization chamber (Ph. Eur. 2.2.66)	- principal peak at 0.511MeV and 1.077MeV, possible sum peak at 1,022MeV − 62–74 minutes	506 kEv 66.33 min	518 kEv 69.31 min	492 kEv 64.42 min
pH value	pH strips (Ph. Eur. 4.1.1 1178900 and 2.2.4)	5.0–8.0	6.5	6.5	6.5
Sterility	Direct inoculation (Ph. Eur. 2.6.1 + 0125)	Sterile	Complies	Complies	Complies
Bacterial endotoxins	LAL-test (Ph. Eur. 2.6.14)	< 15 EU/mL	< 5 EU/mL	< 5 EU/mL	< 5 EU/mL
Radionucleidic purity - ⁶⁸Ga - ⁶⁸Ge and γ-emitted impurities	γ-Spectrometry (Ph. Eur. 2.2.66 + 0125)	- ≥99.9% - ≤0.001%	99.999999983% 0.000000017%	99,999999998% 0,0000000015%	99.999999576% 0.0000004241%
Radiochemical purity - [⁶⁸Ga]Ga -PentixaFor - ⁶⁸Ga³⁺chloride - [⁶⁸Ga]Ga -PentixaFor - ⁶⁸Ga³⁺chloride and ⁶⁸Ga in colloidal forms	HPLC (Ph. Eur. 2.2.29) ITLC (Ph. Eur. 2.2.27)	- ≥95% - ≤2% - ≥95% - ≤2% - ≤3%	99.78% 0.22% 98.81% 0.42% 0.77%	99.76% 0.24% 99.16% 0.85% 0.56%	99.93% 0.07% 99.31% 0.20% 0.49%
Filter integrity test	Non-destructive test (Ph. Eur. 5.1.1)	Bubble point measurement (> 3450 mbar)	Complies	Complies	Complies
Radioactivity	Ionization chamber (Ph. Eur. 2.2.66)	200–1400 MBq	586 MBq	661 MBq	594 MBq
Specific Activity	-	-	11.72 MBq/µg	13.22 MBq/µg	11.88 MBq/µg

All three batches fulfilled the requirements for injectable radiopharmaceutical products regarding the European Pharmacopeia.

Stability assessment

We performed both iTLC and HPLC methods in order to determine the evolution of the RCP after the syntheses. Free Ga³⁺ and, if applicable, colloidal forms measurements were carried out every hour during 4 hours in triplicate, as shown in Table 4 and 5, and Figs. 3, 4 and 5 below.

Table 4

Radiochemical purity assessed using iTLC method during 4 hours
RCP using iTLC method
		Batch 1	Batch 2	Batch 3
Final vial radioactivity		586 MBq	661 MBq	594 MBq
T = 0h	RCP	99.04% 98.81% 98.59%	99.33% 99.09% 99.06%	99.40% 99.24% 99.28%
	Colloidal forms	0.57% 0.66% 1.07%	0.53% 0.65% 0.49%	0.39% 0.46% 0.62%
	Free Ga³⁺	0.39% 0.53% 0.34%	0.14% 0.26% 0.45%	0.21% 0.30% 0.10%
T = 1h	RCP	99.40% 99.05% 98.92%	99.51% 99.51% 99.49%	99.57% 99.40% 99.52%
	Colloidal forms	0.57% 0.67% 0.84%	0.12% 0.13% 0.12%	0.23% 0.58% 0.33%
	Free Ga³⁺	0.03% 0.28% 0.24%	0.37% 0.36% 0.39%	0.20% 0.02% 0.15%
T = 2h	RCP	99.57% 99.03% 99.28%	99.59% 99.32% 99.46%	99.66% 99.61% 99.89%
	Colloidal forms	0.08% 0.57% 0.64%	0.06% 0.36% 0.16%	0.20% 0.25% 0.06%
	Free Ga³⁺	0.35% 0.40% 0.08%	0.35% 0.32% 0.38%	0.14% 0.14% 0.05%
T = 3h	RCP	99.09% 99.67% 99.54%	99.40% 99.49% 99.31%	99.69% 99.36% 99.71%
	Colloidal forms	0.840% 0.25% 0.05%	0.41% 0.46% 0.55%	0.29% 0.41% 0.26%
	Free Ga³⁺	0.07% 0.08% 0.41%	0.19% 0.05% 0.14%	0.02% 0.23% 0.03%
T = 4h	RCP	99.95% 99.62% 99.58%	98.53% 99.44% 99.50%	99.53% 99.37% 99.45%
	Colloidal forms	0.02% 0.28% 0.40%	1.27% 0.52% 0.01%	0.21% 0.54% 0.15%
	Free Ga³⁺	0.03% 0.10% 0.02%	0.20% 0.04% 0.49%	0.26% 0.09% 0.40%

Figure 4. Evolution of impurities (colloidal forms and free Ga³⁺ percentages, assessed by iTLC) after synthesis

Table 5

Radiochemical purity assessed using HPLC method during 4 hours
RCP using HPLC method
		Batch 1	Batch 2	Batch 3
Final vial radioactivity		586 MBq	661 MBq	594 MBq
T = 0h	RCP	99.68% 99.82% 99.84%	99.77% 99.84% 99.68%	99.95% 99.95% 99.89%
T = 0h	Free Ga³⁺	0.32% 0.18% 0.16%	0.23% 0.16% 0.32%	0.05% 0.05% 0.11%
T = 1h	RCP	99.85% 99.82% 99.98%	99.80% 99.81% 99.78%	99.94% 99.87% 99.84%
T = 1h	Free Ga³⁺	0.15% 0.18% 0.025%	0.20% 0.19% 0.22%	0.06% 0.13% 0.16%
T = 2h	RCP	99.91% 99.95% 99.97%	99.91% 99.85% 99.88%	99.83% 99.80% 99.87%
T = 2h	Free Ga³⁺	0.09% 0.05% 0.03%	0.09% 0.15% 0.12%	0.17% 0.20% 0.13%
T = 3h	RCP	99.90% 99.85% 99.86%	99.76% 99.70% 99.81%	99.83% 99.88% 99.77%
T = 3h	Free Ga³⁺	0.10% 0.15% 0.14%	0.24% 0.30% 0.19%	0.17% 0.12% 0.23%
T = 4h	RCP	99.98% 99.95% 99.98%	99.87% 99.73% 99.94%	99.90% 99.85% 99.70%
T = 4h	Free Ga³⁺	0.02% 0.05% 0.02%	0.13% 0.27% 0.06%	0.10% 0.15% 0.30%

All three batches were considered stable as their RCP proved to be superior to 98.5% during 4 hours after the syntheses.

There are already several radio syntheses of [⁶⁸Ga]Ga-PentixaFor described in the literature, using the Scintomics GRP Automated Synthesis Module (Scintomics GmbH) (11, 12), or the Modular Lab PharmTracer (Eckert & Ziegler) (13). However, there are none describing the synthesis using the Gaia/Luna Elysia-Raystest module to our knowledge. The advantage of using this module consists in particular in the concentration of the radioactivity in the SCX cartridge at the beginning of the synthesis, which allows us to control the volumetric activity of the reaction mixture.

Moreover, the radiolabeling efficiencies in the literature were found to be around 70–80%, which is a little lower than what we obtained with our process (average labeling efficiency of 86.96%, n = 3). However, the low number of batches produced does not allow us to have much perspective. The average radiochemical purity was 99.09% (n = 3), which is comparable with the existing literature previously cited. The number of syntheses is however very small, but is sufficient in regard with the European Pharmacopoeia, and could be increased afterward.

As it is, our synthesis method is suitable for clinical use, fulfilling all European Pharmacopeia requirements dealing with injectable radiopharmaceutical drugs. In the near future, the synthesis process may be used in a clinical human trial in our hospital, and later for diagnostic purposes. For example, [⁶⁸Ga]Ga-PentixaFor could become an interesting radiotracer in the determination of the laterality of aldosterone secretion in patients with primary aldosteronism (17). In this indication, PET imaging could become an interesting non-invasive tool versus the current gold-standard protocol, which consists in an adrenal vein sampling performance (18). Moreover, in parallel with labeling with gallium 68, this vector can be labelled with lutetium 177, which allow the development of theragnostic with this molecule (19, 20).

The [⁶⁸Ga]-PentixaFor synthesis process that we had developed on the Gaia/Luna Elysia-Raytest module showed a high radiochemical purity (> 98%) with a good radiolabelling efficacy (> 85%). The radiotracer can be considered as chemically stable during 4 hours after the synthesis, which is suitable for clinical use in routine. The microbiological quality is also good and allows injection in human being. The synthesis fulfilled all acceptance criteria for injectable radiopharmaceutical products regarding the European Pharmacopeia. After validation by the competent health authorities, the [⁶⁸Ga]Ga-PentixaFor may be used in our hospital to assess the laterality of aldosterone secretion in patients with primary aldosteronism, or in hematopoietic malignancies.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availabilty of data and material

The datasets generated or analyzed during the current study are included in this published article. Supplementary information are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

The authors received no financial support for the current study. The PentixaPharm laboratory graciously donated the peptides: [⁶⁹Ga]-Pentixafor acetate and GMP-grade Pentixafor.

Authors' contributions

TD and YM: study conception and design, data collection, analysis and interpretation of results, and manuscript redaction. CBR: review of the article and revision for significant intellectual content. JC, RB: review of the article. All authors read and approved the final manuscript.

Acknowledgements

Authors would like to thanks the PentixaPharm laboratory for the gift of the peptides, and in particular Jens Kaufman for his help.

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PTXGMP1.pdf
Supplementary file 1: GMP-conditions synthesis report N°1 This document shows all details dealing with technique parameters of the Gaia/Luna Elysia-Raytest module during the first GMP-condition synthesis.
PTXGMP2.pdf
Supplementary file 2: GMP-conditions synthesis report N°2 This document shows all details dealing with technique parameters of the Gaia/Luna Elysia-Raytest module during the second GMP-condition synthesis.
PTXGMP3.pdf
Supplementary file 3: GMP-conditions synthesis report N°3 This document shows all details dealing with technique parameters of the Gaia/Luna Elysia-Raytest module during the third GMP-condition synthesis.

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published 07 Feb, 2023

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Editorial decision: Major revision
23 Dec, 2022
Reviewers agreed at journal
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Automated synthesis and quality control of [68Ga]Ga-PentixaFor using the Gaia/Luna Elysia-Raytest module for CXCR4 PET imaging

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Journal Publication

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Abstract

Background

Results

Conclusion

Figures

Background

Methods

Reagents and devices

Description of the manufacturing process

Radiolabeling efficiency

Optimization of the synthesis settings

Validation and process controls of GMP-quality batches

Appearance and pH

Chemical identity

Radionuclear identity

Radiochemical purity

Radionucleidic purity

Bacterial endotoxins

Radiochemical stability

Results

Final composition

Optimization of synthesis settings

Validation and quality control of GMP-quality batches

Stability assessment

Discussion

Conclusion

Declarations

References

Supplementary Files

Status:

Journal Publication

Version 1