Everolimus Reduces (89)Zr-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 (89)Zr-bevacizumab PET scans before and at 2 and 12 wk during everolimus treatment. (89)Zr-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 (89)Zr-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).


CONCLUSIONS
This study demonstrates variable (89)Zr-bevacizumab PET tumor uptake in NET patients. (89)Zr-bevacizumab tumor uptake diminished during everolimus treatment. Serial (89)Zr-bevacizumab PET might be useful as an early predictive biomarker of anti-VEGF-directed treatment in NET patients.
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Sophie J
SJ
van Asselt
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Sjoukje F
SF
Oosting
Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Adrienne H
AH
Brouwers
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; and.
Alfons H H
AH
Bongaerts
Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Johan R
JR
de Jong
Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands Department of Hospital and Clinical Pharmacy, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Marjolijn N
MN
Lub-de Hooge
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Thijs H
TH
Oude Munnink
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Helle-Brit
HB
Fiebrich
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Wim J
WJ
Sluiter
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Thera P
TP
Links
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Annemiek M E
AM
Walenkamp
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands e.g.e.de.vries@umcg.nl.
Elisabeth G E
EG
de Vries
D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000378:metabolism*; D000068258:Bevacizumab; D001692:Biological Transport / Q000187:drug effects; D053379:Chromogranin A / Q000097:blood; D000068338:Everolimus; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011868:Radioisotopes; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology; D015040:Zirconium
D061067:Antibodies, Monoclonal, Humanized; D053379:Chromogranin A; D011868:Radioisotopes; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000068338:Everolimus; C580636:89Zr-bevacizumab; D015040:Zirconium; D020123:Sirolimus
89Zr-bevacizumab PET; VEGF-A; biomarker; everolimus; neuroendocrine tumors