Page 77 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Initial clinical trials with 89Zr-immuno-PET in oncology
expression and tumor uptake of the mAb. The fact that VEGF-A is not/hardly expressed in normal tissue, while the antigen might be well accessible for mAbs in tumor tissue, might be favorable factors for finding such a correlation. This observation opens avenues for the use of 89Zr-bevacizumab-PET for response monitoring in therapeutic strategies aiming to downregulate VEGF-A.
The effect of the HSP90 inhibitor NVP-AUY922 on alteration of VEGF-A
status was evaluated in the same study discussed earlier for 89Zr-trastuzumab in
breast cancer (24). However, 89Zr-bevacizumab-PET was not able to predict
treatment outcome measured by CT in patients with estrogen-receptor-positive
breast cancer (n=6). 4
89Zr-labeled bevacizumab in lung cancer
Bevacizumab is also used for treatment of non-small cell lung carcinoma and 89Zr- bevacizumab is a potential predictive imaging biomarker for this patient group. In a pilot study it was evaluated whether tumor uptake of 89Zr-bevacizumab could be visualized and quantified in 7 patients with lung cancer (28). Moreover, in this study the correlation between tumor uptake of 89Zr-bevacizumab and response to a bevacizumab-based treatment regimen was explored. 89Zr-bevacizumab PET was performed at day 4 and 7 after injection of 37 MBq 89Zr-labeled bevacizumab (5 mg), one week prior to start of induction therapy with carboplatin, paclitaxel and bevacizumab (15 mg/kg), followed by bevacizumab maintenance upon non- progression after 4 cycles.
All tumor lesions showed visible 89Zr-bevacizumab uptake. Tumor-to- blood ratios increased from 1.23 ± 0.4 to 2.2 ± 1.2 between day 4 and 7 p.i.. Tumor lesions had an approximately four times higher 89Zr-bevacizumab uptake compared to non-tumor background tissues (muscle, healthy lung and fatty tissue). A positive trend, but no significant correlation, was observed for tumor uptake and progression-free survival and overall survival after combined chemo- immunotherapy.
A limitation of this study design is that no distinction is possible between therapeutic contribution of chemotherapy and immunotherapy, as this is a combined treatment regimen. Therefore, further 89Zr-bevacizumab-PET studies are required to assess VEGF-target status after combination treatment, as a response predictor for effectiveness of subsequent bevacizumab maintenance therapy.
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