89Zr-bevacizumab PET visualizes heterogeneous tracer accumulation in tumor lesions of renal cell carcinoma patients and differential effects of antiangiogenic treatment.

Abstract

UNLABELLED:

No validated predictive biomarkers for antiangiogenic treatment of metastatic renal cell carcinoma (mRCC) exist. Tumor vascular endothelial growth factor A (VEGF-A) level may be useful. We determined tumor uptake of (89)Zr-bevacizumab, a VEGF-A-binding PET tracer, in mRCC patients before and during antiangiogenic treatment in a pilot study.

METHODS:

Patients underwent (89)Zr-bevacizumab PET scans at baseline and 2 and 6 wk after initiating either bevacizumab (10 mg/kg every 2 wk) with interferon-α (3-9 million IU 3 times/wk) (n = 11) or sunitinib (50 mg daily, 4 of every 6 wk) (n = 11). Standardized uptake values were compared with plasma VEGF-A and time to disease progression.

RESULTS:

(89)Zr-bevacizumab PET scans visualized 125 evaluable tumor lesions in 22 patients, with a median SUV(max) (maximum standardized uptake value) of 6.9 (range, 2.3-46.9). Bevacizumab/interferon-α induced a mean change in tumor SUV(max) of -47.0% (range, -84.7 to +20.0%; P < 0.0001) at 2 wk and an additional -9.7% (range, -44.8 to +38.9%; P = 0.015) at 6 wk. In the sunitinib group, the mean change in tumor SUV(max) was -14.3% at 2 wk (range, -80.4 to +269.9; P = 0.006), but at 6 wk the mean change in tumor SUV(max) was +72.6% (range, -46.4 to +236%; P < 0.0001) above baseline. SUV(max) was not related to plasma VEGF-A at all scan moments. A baseline mean tumor SUV(max) greater than 10.0 in the 3 most intense lesions corresponded with longer time to disease progression (89.7 vs. 23.0 wk; hazard ratio, 0.22; 95% confidence interval, 0.05-1.00).

CONCLUSION:

Tumor uptake of (89)Zr-bevacizumab is high in mRCC, with remarkable interpatient and intrapatient heterogeneity. Bevacizumab/interferon-α strongly decreases tumor uptake whereas sunitinib results in a modest reduction with an overshoot after 2 drug-free weeks. High baseline tumor SUV(max) was associated with longer time to progression.

• Authors: Sjoukje F Oosting, Adrienne H Brouwers, Suzanne C van Es, Wouter B Nagengast, Thijs H Oude Munnink, Marjolijn N Lub-de Hooge, Harry Hollema, Johan R de Jong, Igle J de Jong, Sanne de Haas, Stefan J Scherer, Wim J Sluiter, Rudi A Dierckx, Alfons H H Bongaerts, Jourik A Gietema, Elisabeth G E de Vries
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 56 Issue 1 Pg. 63-9 (Jan 2015) ISSN: 1535-5667 [Electronic] United States
• PMID: 25476536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized
• Indoles
• Interferon-alpha
• Pyrroles
• Radioactive Tracers
• Radioisotopes
• Vascular Endothelial Growth Factor A
• Bevacizumab
• 89Zr-bevacizumab
• Zirconium
• Sunitinib

Topics

• Aged
• Angiogenesis Inhibitors (therapeutic use)
• Antibodies, Monoclonal, Humanized (metabolism, therapeutic use)
• Bevacizumab
• Biological Transport
• Carcinoma, Renal Cell (blood, diagnostic imaging, drug therapy, metabolism)
• Female
• Humans
• Indoles (therapeutic use)
• Interferon-alpha (therapeutic use)
• Kidney Neoplasms (blood, diagnostic imaging, drug therapy, metabolism)
• Male
• Middle Aged
• Pyrroles (therapeutic use)
• Radioactive Tracers
• Radioisotopes
• Radionuclide Imaging
• Sunitinib
• Treatment Outcome
• Vascular Endothelial Growth Factor A (blood)
• Zirconium