Page 79 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Initial clinical trials with 89Zr-immuno-PET in oncology
Further studies are required to assess whether baseline tumor uptake of 89Zr-bevacizumab can be used to predict benefit from anti-angiogenic treatment. Heterogeneity in tumor uptake of 89Zr-bevacizumab may offer a possibility to differentiate patients groups based on tumor biology and to guide the choice between anti-angiogenic and other treatment strategies.
89Zr-labeled bevacizumab in neuroendocrine tumors
In another feasibility study with 89Zr-bevacizumab, the effect of everolimus, a mammalian target of rapamycin inhibitor, on tumor uptake was investigated in
patients with advanced progressive neuroendocrine tumors (NET) (30). As 4 everolimus can reduce VEGF-A production, it was evaluated whether NET lesions
can be visualized by 89Zr-bevacizumab PET and whether tumor uptake of 89Zr- bevacizumab decreases from baseline to week 2 and 12 during everolimus therapy
(10 mg orally once daily). This study was also performed with 37 MBq 89Zr-labeled bevacizumab (5 mg), with imaging 4 days p.i.. In 4 of 14 patients no tumor lesions
could be visualized with 89Zr-bevacizumab-PET, in the remaining patients only
19% of tumor lesions ≥ 1 cm (63 lesions in total) known by CT were positive at
PET, demonstrating variable 89Zr-bevacizumab tumor uptake in NET patients. 89Zr-bevacizumab uptake diminished during everolimus treatment with a mean of
-7% at 2 weeks and -35% at 12 weeks. Change in tumor uptake correlated with
treatment outcome, assessed by CT after 3 months. There was no correlation
between baseline tumor uptake and change of tumor size as assessed by CT,
indicating that 89Zr-bevacizumab-PET was not qualified for response prediction
before therapy.
Interestingly, in 4 of 14 patients no visual uptake was observed, while no patient had progressive disease after 3 and 6 months of treatment with everolimus. This might indicate that everolimus exerts also other mechanisms of action than just reduction of VEGF-A, or reflect that NETs are slow growing tumors.
89Zr-labeled bevacizumab in pontine glioma
For brain tumors like diffuse intrinsic pontine glioma in children, it is not known whether targeted drugs actually can reach the tumor. Nevertheless, several studies are ongoing to investigate treatment with bevacizumab for this indication. The first report ever on molecular imaging in children, was a feasibility study on the therapeutic potential of bevacizumab and toxic risks, due to VEGF-A expression in normal organs in children with pontine glioma (31). 3 patients, aged 6, 7 and 17
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