PT  - JOURNAL ARTICLE
AU  - Dijkers, Eli C.F.
AU  - Kosterink, Jos G.W.
AU  - Rademaker, Anna P.
AU  - Perk, Lars R.
AU  - van Dongen, Guus A.M.S.
AU  - Bart, Joost
AU  - de Jong, Johan R.
AU  - de Vries, Elisabeth G.E.
AU  - Lub-de Hooge, Marjolijn N.
TI  - Development and Characterization of Clinical-Grade <sup>89</sup>Zr-Trastuzumab for HER2/<em>neu</em> ImmunoPET Imaging
AID  - 10.2967/jnumed.108.060392
DP  - 2009 Jun 01
TA  - Journal of Nuclear Medicine
PG  - 974--981
VI  - 50
IP  - 6
4099  - http://jnm.snmjournals.org/content/50/6/974.short
4100  - http://jnm.snmjournals.org/content/50/6/974.full
SO  - J Nucl Med2009 Jun 01; 50
AB  - 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 89Zr-trastuzumab was compared with the SPECT tracer 111In-trastuzumab, which we have tested in the clinic already. Methods: Trastuzumab was labeled with 89Zr and (for comparison) with 111In. 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 89Zr 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 μg) proved to be optimal for imaging. The comparative biodistribution study showed a higher level of 89Zr-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 89Zr-trastuzumab and 111In-trastuzumab uptake in tumors (R2 = 0.972). Conclusion: Clinical-grade 89Zr-trastuzumab showed high and HER2/neu-specific tumor uptake at a good resolution.