Human dosimetry of ⁸⁹Zr-trastuzumab-PET in patients with HER2-positive breast cancer

Objectives Human epidermal growth factor receptor 2 (HER2) is expressed in approximately 25% of all breast cancers; its overexpression is associated with more aggressive disease. In vivo measurement of HER2 expression offers several advantages, including the ability to assess HER2 expression in all parts of the tumor and in multiple lesions, many of which may be inaccessible to biopsy; to assess in vivo availability of HER2; and to monitor therapeutic effects on HER2 expression. The objective of this study was to estimate radiation dosimetry with ⁸⁹Zr-trastuzumab and to determine the optimal imaging time in patients with HER2-positive breast cancer.

Methods ⁸⁹Zr-trastuzumab was prepared as in[1,2]. Eleven women with biopsy-proven HER2-positive breast cancer were injected with ~2 mCi of ⁸⁹Zr-trastuzumab and underwent PET/CT twice between 0 and 6 days after administration. Trastuzumab-naïve patients received 50 mg trastuzumab and patients under trastuzumab therapy received 10 mg, typically 30 min to 2 hours before ⁸⁹Zr-trastuzumab injection. Images were reconstructed with 3D OSEM, 3it/21subsetsand Gaussian smoothing of 7 mm. Pharmacokinetic data were obtained from whole-torso PET images and organ time-activity curves were created by collating data from all patients. Human dosimetry estimates were obtained from the residence times and OLINDA with the adult female model.

Results High-quality images and best tumor-to-nontumor contrast were achieved on the images acquired at 5 ± 1 day after injection. The tracer was predominantly retained in the liver (~15% ID versus ~5% ID based on animal data), remaining constant over time, and the liver thus was the critical organ with a dose of 1.54 mSv/MBq (5.68 rad/mCi). Theeffective dose was 0.47 mSv/MBq (1.74 rem/mCi).

Conclusions The best imaging time is at least 4 days after administration of ⁸⁹Zr-trastuzumab. The radiation dose to the liver was greater than calculated using animal dosimetry data.

Research Support This work was supported by the NIH by 1R21CA182945-01