Table 2 QC specifications and validation results of [18F]SFB and [18F]FB-IL2 synthesis
From: Clinical-grade N-(4-[18F]fluorobenzoyl)-interleukin-2 for PET imaging of activated T-cells in humans
Test | Specification | Justification | Batch 1 | Batch 2 | Batch 3 | Batch 4 |
|---|---|---|---|---|---|---|
[18F]SFB | ||||||
Appearance | Clear, colorless | Ph. Eur. | clear, colorless | clear, colorless | clear, colorless | clear, colorless |
Minimum yield | > 2 GBq | Minimum amount required to produce a patient dose of [18F]FB-IL2 | 20.2 GBq | 19 GBq | 19.5 GBq | 12.4 GBq |
Radiochemical purity | > 90% | Adequate purity for a starting material in the conjugation reaction | 96.0% | 94.9% | 95.7% | 99.9% |
[18F]FB-IL2 | ||||||
Appearance | Clear, colorless | Ph. Eur. | clear, colorless | clear, colorless | clear, colorless | clear, colorless |
PH | 4–7 | Ph. Eur | 4.5 | 5 | 4.5 | 7 |
Radiochemical identity: | Standard requirement | |||||
- retention time IL2 (UPLC) | - ca. 9 min | - 8.9 min | - 9.0 min | - 8.9 min | - 9.0 min | |
- retention time [18F]FB-IL2 (UPLC) | - IL2 standard + 0.6–1.0 min | - 9.6 min | - 9.7 min | - 9.8 min | - 9.5 min | |
Radiochemical purity | > 95% | Ph. Eur. | 97.1% | 97.4% | 95.7% | 98.0% |
Radionuclide purity | > 99% | Ph. Eur. | > 99% | > 99% | > 99% | > 99% |
Radionuclide identity | T1/2 110 min; acceptable range 105–115 min | Ph. Eur. | 115 min | 115 min | 112 min | 112 min |
Energy 511 keV | 511 keV | 511 keV | 511 keV | 511 keV | ||
[18F]FB-IL2 concentration | < 5 mg/L | Corresponds to a max dose of 50 μg (3 nmol) for a standard injection volume of 10 mL | < 3.7 mg/L1 | < 3.7 mg/L | < 3.7 mg/L | < 3.7 mg/L |
Unknown impurities | < 1 mg/L | < 1 mg/L | < 1 mg/L | - < 1 mg/L | < 1 mg/L | |
Molar activity | > 50,000 MBq/μmol | Corresponds with mass dose [18F]FB-IL2 of 50 μg at an injected dose of 200 MBq | > 50,000 MBq/μmol | > 50,000 MBq/μmol | > 50,000 MBq/μmol | > 50,000 MBq/μmol |
Filter integrity (pressure hold test/bubble point test) | > 3.4 bar | Conforms to filter manufacturer’s recommendations | > 3.4 bar | > 3.4 bar | > 3.4 bar | > 3.4 bar |
Sterility | Sterile2 | Ph. Eur. 2.6.1 | sterile | sterile | sterile | sterile |
Endotoxins | < 2.5 EU/mL | Ph. Eur. 2.6.14 | < 0.5 EU/mL | < 0.5 EU/mL | < 0.5 EU/mL | < 1.0 EU/mL |
Kryptofix 222 | < 25 mg/L | Ph. Eur. | < 25 mg/L | < 25 mg/L | < 25 mg/L | < 25 mg/L |
Osmolarity | < 3000 mOsmol/kg2 | Ph. Eur. 2.2.35 Based on formulation | 2760 mosmol/kg | 2940 mosmol/kg | 2583 mosmol/kg | 2790 mosmol/kg |
Acetonitrile | < 410 mg/L2 | Ph. Eur. 2.4.24 | < 10 mg/L | < 10 mg/L | < 10 mg/L | < 10 mg/L |
DMF | < 880 mg/L2 | Ph. Eur. 2.4.24 | < 200 mg/L | < 200 mg/L | < 200 mg/L | < 200 mg/L |
Ethanol | < 150 g/L2 | Based on formulation | 87.7 g/L | 102.7 g/L | 88.0 g/L | 105 g/L |