Page 78 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 4
As all lesions were visualized with a total protein dose of 5 mg 89Zr- bevacizumab, and no targeting of normal tissues became apparent, there is no indication of an antigen sink for this mAb. A limitation of the current study was that no extra biopsies were obtained to confirm VEGF-A tumor expression as driver for 89Zr-bevacizumab uptake and therapeutic response. In order to provide more insight in the effect of perfusion, additional imaging of perfusion may be considered in further studies. For such studies, the authors also suggest not to include small tumor lesions in which PET quantification would suffer from partial volume effects.
89Zr-labeled bevacizumab in renal cell carcinoma
Oosting et al. investigated 89Zr-bevacizumab-PET in patients with metastatic renal cell carcinoma as an imaging modality for treatment evaluation of anti-angiogenic drugs (29).
Patients were randomized between treatment with bevacizumab (10 mg/kg intravenously every 14 days) combined with interferon-α (3 million IU, 3 times per week) (n=11) or sunitinib (50 mg orally, daily for 4 weeks followed by 2 weeks off treatment) (n=11), which is a multi-targeted receptor tyrosine kinase inhibitor. At baseline, and 2 and 6 weeks after treatment, PET scans were acquired after administration of 37 MBq 89Zr-labeled bevacizumab (5 mg).
Tumor lesions were visualized in all patients (in total 125 lesions), including 35 that had not been detected at CT. 19 lesions were outside the field of view of the CT, including 5 brain lesions in 3 patients (two had known brain metastasis). Remarkable interpatient and intrapatient heterogeneity in tumor uptake of 89Zr- bevacizumab was observed. A strong decrease in tumor uptake of -47.0 % at week 2 was observed for patients on bevacizumab/interferon-α treatment, with an additional change of -9.7 % at week 6. For patients on sunitinib treatment, a mean change in tumor uptake of -14.3 % at week 2 and a rebound of +72.6 % at week 6 was reported (after 2 drug-free weeks).
Change in tumor uptake of 89Zr-bevacizumab did not correlate with time to progression. Baseline tumor uptake of 89Zr-bevacizumab corresponded with longer time to progression. Although reduced 89Zr-bevacizumab tumor uptake after treatment might be caused by saturation due to treatment with unlabeled bevacizumab, other clinical studies have suggested that bevacizumab-induced vascular changes do occur after treatment.
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