Everolimus Reduces 89Zr-Bevacizumab Tumor Uptake in Patients with Neuroendocrine Tumors

Everolimus increases progression-free survival in patients with advanced neuroendocrine tumors (NETs). Currently, no biomarkers are available for early selection of patients who will benefit from everolimus. Everolimus can reduce vascular endothelial growth factor A (VEGF-A) production by tumor cells. Therefore, we aimed to investigate the effect of everolimus on tumor uptake of the radioactive-labeled VEGF-A antibody bevacizumab with PET in NET patients. Methods: Patients with advanced progressive well-differentiated NETs underwent Zr-89-bevacizumab PET scans before and at 2 and 12 wk during everolimus treatment. Zr-89-bevacizumab uptake was quantified by the maximum standardized uptake value (SUVmax). Tumor response and the percentage change in the sum of target lesion diameters were determined according to Response Evaluation Criteria in Solid Tumors 1.1 on CT (3 monthly). Results: In 4 of the 14 patients entered, no tumor lesions were visualized with Zr-89-bevacizumab PET. In the remaining patients, 19% of tumor lesions 1 cm or greater known by CT were visualized. Tumor SUVmax decreased during everolimus treatment, with a median of -7% at 2 wk (P = 0.09) and a median of -35% at 12 wk (P < 0.001). The difference in SUVmax at 2 and 12 wk with respect to SUVmax, at baseline correlated with percentage change on CT at 6 mo (r(2) = 0.51, P < 0.05, and r(2) = 0.61, P < 0.01, respectively). Conclusion: This study demonstrates variable Zr-89-bevacizumab PET tumor uptake in NET patients. Zr-89-bevacizumab tumor uptake diminished during everolimus treatment. Serial Zr-89-bevacizumab PET might be useful as an early predictive biomarker of anti-VEGF-directed treatment in NET patients.