89Zr-Bevacizumab PET: Potential Early Indicator of Everolimus Efficacy in Patients with Metastatic Renal Cell Carcinoma

J Nucl Med. 2017 Jun;58(6):905-910. doi: 10.2967/jnumed.116.183475. Epub 2017 Jan 12.

Abstract

Currently, biomarkers that predict the efficacy of everolimus in metastatic renal cell carcinoma (mRCC) patients are lacking. Everolimus inhibits vascular endothelial growth factor A (VEGF-A) expression. We performed PET scans on mRCC patients with 89Zr-bevacizumab, a VEGF-A-binding antibody tracer. The aims were to determine a change in tumor tracer uptake after the start of everolimus and to explore whether 89Zr-bevacizumab PET can identify patients with early disease progression. Methods:89Zr-bevacizumab PET was done before and 2 and 6 wk after the start of everolimus, 10 mg/d, in mRCC patients. Routine CT scans were performed at baseline and every 3 mo thereafter. Tumor tracer uptake was quantified using SUVmax The endpoints were a change in tumor tracer uptake and treatment response on CT after 3 mo. Results: Thirteen patients participated. The median SUVmax of 94 tumor lesions was 7.3 (range, 1.6-59.5). Between patients, median tumor SUVmax varied up to 8-fold. After 2 wk, median SUVmax was 6.3 (1.7-62.3), corresponding to a mean decrease of 9.1% (P < 0.0001). Three patients discontinued everolimus early. At 6 wk, a mean decrease in SUVmax of 23.4% compared with baseline was found in 70 evaluable lesions of 10 patients, with a median SUVmax of 5.4 (1.1-49.4, P < 0.0001). All 10 patients who continued treatment had stable disease at 3 mo. Conclusion: Everolimus decreases 89Zr-bevacizumab tumor uptake. Further studies are warranted to evaluate the predictive value of 89Zr-bevacizumab PET for everolimus antitumor efficacy.

Trial registration: ClinicalTrials.gov NCT01028638.

Keywords: biomarker; everolimus; molecular imaging; positron emission tomography; renal cell carcinoma.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bevacizumab*
  • Carcinoma, Renal Cell / diagnostic imaging
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / secondary*
  • Drug Monitoring / methods
  • Early Detection of Cancer / methods
  • Everolimus / therapeutic use*
  • Female
  • Humans
  • Kidney Neoplasms / diagnostic imaging*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods
  • Prognosis
  • Radioisotopes
  • Radiopharmaceuticals
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Treatment Outcome
  • Zirconium

Substances

  • Radioisotopes
  • Radiopharmaceuticals
  • Bevacizumab
  • Everolimus
  • Zirconium

Associated data

  • ClinicalTrials.gov/NCT01028638