Synthesis of Clinical-Grade [18F]-Fluoroestradiol as a Surrogate PET Biomarker for the Evaluation of Estrogen Receptor-Targeting Therapeutic Drug
Table 1
QC results of three batches (FES-MBR-01, FES-MBR-02, and FES-MBR-03).
Quality control test
Description
Acceptance criteria
FES-MBR-01
FES-MBR-02
FES-MBR-03
Particulates and color
Visual inspection for color and particulates
Clear and colorless
Clear
Clear
Clear
Filter integrity
Bubble point test
>50 PSI
55
60
55
pH
pH as per USP pH
pH must be between 6 and 8
7
7
7
Residual Kryptofix 2.2.2a
Color spot test
<50 g/mL Kryptofix 2.2.2 by comparison with standard
<50 g/mL
<50 g/mL
<50 g/mL
Radiochemical purity
Radiochemical purity > 95%
97.8
99.7
99.9
FES (g per 12 mCi dose)
HPLCb, consistent with guidelines of USP
≤5 g per dose
0.72
1.68
1.58
Other UV impurities g/mL (g/dose)
≤5 g per dose
0.30 (3.6)
<0.06 (<1.7)
<0.06 (<1.7)
Radiochemical purity
TLC
> 0.5 and purity ≥ 95%
0.8 and 98.6
0.8 and 96.6
0.7 and 96.9
Residual solvent levelsc
Gas chromatography
Acetone < 5,000 ppm Acetonitrile < 400 ppm
<3125 <250
<3125 <250
<3125 <250
Radionuclidic purity
Half-life determination
105–120 minutes
110
111
110
Bacterial endotoxin levels
Limulus amoebocyte lysate (LAL) by gel clot or PTS
<175 EU per dose
<2
<2
<2
*Sterility test (14 days)
USP sterility test (USP )
No growth
No growth
No growth
No growth
aKryptofix (K2.2.2) content was determined with the TLC spot test as per USP guidelines (TLC solvent: 9 : 1 solution of methanol and 30% ammonium hydroxide (v : v); TLC material: silica 60, = 0.1; Kryptofix standard solution for visual testing: 50 g/mL; TLC development: iodine chamber).
bPhenomenex Gemini C18 reversed-phase HPLC column with a mobile phase of 50% ethanol : 50% water (v : v). The column flow rate is 0.5 mL/min.
cAcetone < 5,000 ppm and acetonitrile < 400 ppm as per USP Organic Volatile Impurities.
*Not a release criterion.
