Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 50, Issue 6, Pages 974-981Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.108.060392
Keywords
HER2/neu; immunoPET; imaging; breast cancer
Funding
- Dutch Cancer Society [2007- 3739]
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The anti-human epidermal growth factor receptor 2 (HER2/neu) antibody trastuzumab is administered to patients with HER2/neu-overexpressing breast cancer. Whole-body noninvasive HER2/neu scintigraphy could help to assess and quantify the HER2/neu expression of all lesions, including nonaccessible metastases. The aims of this study were to develop clinical-grade radiolabeled trastuzumab for clinical HER2/neu immunoPET scintigraphy, to improve diagnostic imaging, to guide antibody-based therapy, and to support early antibody development. The PET radiopharmaceutical Zr-89-trastuzumab was compared with the SPECT tracer In-111-trastuzumab, which we have tested in the clinic already. Methods: Trastuzumab was labeled with Zr-89 and (for comparison) with In-111. The minimal dose of trastuzumab required for optimal small-animal PET imaging and biodistribution was determined with human HER2/neu-positive or -negative tumor xenograft-bearing mice. Results: Trastuzumab was efficiently radiolabeled with Zr-89 at a high radiochemical purity and specific activity. The antigen-binding capacity was preserved, and the radiopharmaceutical proved to be stable for up to 7 d in solvent and human serum. Of the tested protein doses, the minimal dose of trastuzumab (100 mu g) proved to be optimal for imaging. The comparative biodistribution study showed a higher level of Zr-89-trastuzumab in HER2/neu-positive tumors than in HER2/neu-negative tumors, especially at day 6 (33.4 +/- 7.6 [mean +/- SEM] vs. 7.1 +/- 0.7 percentage injected dose per gram of tissue). There were good correlations between the small-animal PET images and the biodistribution data and between Zr-89-trastuzumab and In-111-trastuzumab uptake in tumors (R-2 = 0.972). Conclusion: Clinical-grade Zr-89-trastuzumab showed high and HER2/neu-specific tumor uptake at a good resolution.
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