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

J Nucl Med. 2015 Jan;56(1):63-9. doi: 10.2967/jnumed.114.144840. Epub 2014 Dec 4.

Abstract

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.

Keywords: bevacizumab; molecular imaging; positron emission tomography; renal cell carcinoma; sunitinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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