Article Figures & Data
Figures
- FIGURE 1.
Summarized stability data obtained at 21°C. The 0.25 M NaOAc buffer containing 5 mg·mL−1 L-MET was superior to other formulations at maintaining solution stability of 89Zr-DFO-cetuximab (A) and 89Zr-DFO-trastuzumab (B) during study. Percentage intact radiopharmaceutical was determined by subtracting total area under product peak from total area generated for all peaks in size-exclusion chromatogram and multiplying by factor of 100%. Each data point is average of 3 size-exclusion chromatography runs.
- FIGURE 2.
Representative PET/CT image of mouse bearing HER2+ and HER2− tumors in contralateral flanks and imaged with 89Zr-DFO-trastuzumab. Coronal (top) and axial (bottom) sections of same mouse were imaged at 144 h. Images were taken from same anatomic location and equally scaled. More radioactivity was retained in HER2+ tumor, suggesting that 89Zr-DFO-trastuzumab remains reactive toward antigen if injected immediately after preparation. Central necrotic core is observed within HER2+ tumor.
- FIGURE 3.
PET/CT data for mice injected with 89Zr-DFO-trastuzumab prepared with 89ZrCl4. (A) Tumor-to-muscle ratios increase as 89Zr-DFO-trastuzumab undergoes clearance from nontarget tissues. (B) At 144 h, more radioactivity is retained in HER2+ tumors, corroborating imaging data.
Tables
89Zr(ox)2 Parameter Perk et al.* Knight et al.† This work 89ZrCl4 in this work mAb (mg)‡ 0.7–3.0 0.1 0.35 0.25 89Zr added (MBq) 37–250 10 40–45 40–45 Oxalic acid neutralization method 2 M Na2CO3 1 M Na2CO3 2 M Na2CO3 None Reaction buffer 0.5 M HEPES¶ PBS§ 0.5 M HEPES¶ 0.5 M HEPES¶ Final reaction pH 6.8–7.2 7–8 6.8–7.2 6.8–7.2 Reaction temperature (°C) 21–24 21–24 21–24 21–24 Reaction time (h) 1 1 1 0.25 Radiolabeling yield (%) >80 96.9 ± 3.3 ≥95ǁ ≥97.5ǁ Radiochemical purity (%) >95 >95 ≥96ǁ ≥97.5ǁ Specific activity (MBq μg−1) 0.067–0.086 0.1 ± 0.03 0.105 ± 0.003 (n = 10)# 0.174 ± 0.003 (n = 10)# ↵* Adapted from (15).
↵† Adapted from (18).
↵‡ Mass mAb used in radiochemical synthesis.
↵¶ pH 7.1–7.3.
↵§ pH 7.4.
↵ǁ Unchelated 89Zr was not present in original reaction mixture as determined by Radio–instant thin-layer chromatography. Final purity and yield reflect presence of high- and low-molecular-weight species, which were additionally determined by size-exclusion chromatography.
↵# 89Zr-DFO-trastuzumab (n = 5) and 89Zr-DFO-cetuximab (n = 5).
PBS = phosphate-buffered saline.
Supplemental Data
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