111In-bevacizumab imaging of renal cell cancer and evaluation of neoadjuvant treatment with the vascular endothelial growth factor receptor inhibitor sorafenib.
Clear cell renal cell cancer (ccRCC) prominently expresses vascular endothelial growth factor-A (VEGF-A), and new treatment strategies for renal cell cancer (RCC) aim at the inhibition of VEGF-VEGF receptor signaling. This study explores the ability of (111)In-bevacizumab scintigraphy to depict RCC and to evaluate response to neoadjuvant treatment with sorafenib, a VEGF receptor inhibitor.


METHODS
The ability to depict RCC with (111)In-bevacizumab scintigraphy was tested in 14 patients scheduled to undergo a tumor nephrectomy; of these, 9 RCC patients were treated in a neoadjuvant setting with sorafenib (400 mg orally twice a day). In the latter group, baseline and posttreatment (111)In-bevacizumab scans were compared. The intratumoral distribution of (111)In-bevacizumab was determined scintigraphically ex vivo in a 1-cm lamella of the resected tumorous kidney. Expression of VEGF-A, glucose transporter-1, carbonic anhydrase IX, α-smooth-muscle actin, and Ki67 was determined by immunohistochemistry and compared with the local concentration of (111)In-bevacizumab. Additionally, the VEGF-A content in tumor samples was determined quantitatively by enzyme-linked immunosorbent assay.


RESULTS
In all 5 non-neoadjuvant-treated patients, preferential accumulation of (111)In-bevacizumab was observed in the tumors. All ccRCC lesions with enhanced (111)In-bevacizumab targeting expressed high levels of VEGF-A. Treatment with sorafenib resulted in a significant decrease of (111)In-bevacizumab uptake in the tumor in the patients with ccRCC (mean change, -60.5%; range, +1.5% to -90.1%). The decrease in uptake was due to destruction of the tumor neovasculature, whereas the VEGF-A expression remained intact. In the patient with papillary RCC, limited uptake without change after sorafenib was observed.


CONCLUSIONS
RCC lesions were clearly delineated with (111)In-bevacizumab scintigraphy. Neoadjuvant treatment with sorafenib resulted in a significant decrease of (111)In-bevacizumab uptake in RCC. (111)In-bevacizumab scintigraphy can be an attractive biomarker for response and needs further study.
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. i.desar@AIG.umcn.nl
Ingrid M E
IM
Desar
Alexander B
AB
Stillebroer
Egbert
E
Oosterwijk
William P J
WP
Leenders
Carla M L
CM
van Herpen
Winette T A
WT
van der Graaf
Otto C
OC
Boerman
Peter F A
PF
Mulders
Wim J G
WJ
Oyen
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use*; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000601:surgery / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007205:Indium Radioisotopes; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000601:surgery / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009392:Nephrectomy; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D000077157:Sorafenib; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates; D007205:Indium Radioisotopes; D010671:Phenylurea Compounds; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor