VEGF-SPECT with In-111-bevacizumab in stage III/IV melanoma patients

Wouter B. Nagengast, Marjolijn N. Lub-de Hooge, Esther M. E. van Straten, Schelto Kruijff, Adrienne H. Brouwers, Wilfred F. A. den Dunnen, Johan R. de Jong, Harry Hollema, Rudi A. Dierckx, Nanno H. Mulder, Elisabeth G. E. de Vries, Harald J. Hoekstra, Geke A. P. Hospers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Purpose: A feasibility study was performed to investigate the presence of VEGF in melanoma lesions by VEGF-SPECT with In-111-bevacizumab. In addition the effect of a single therapeutic bevacizumab dose on In-111-bevacizumab uptake was compared with VEGF levels in resected melanoma lesions.

Patients and methods: Eligible were patients with stage III/IV melanoma who presented with nodal recurrent disease. VEGF-SPECT was performed after administration of 100 Mbq (111) In-bevacizumab (8 mg) at days 0, 2, 4 and 7 post injection. Tumour visualisation and quantification were compared with CT and FDG-PET. On day 7 a single dose of 7.5 mg/kg bevacizumab was administered intravenously. On day 21, a second tracer dose In-111-bevacizumab was administered and scans were obtained on days 21, 25 and 28. Metastases were surgically resected within 2 weeks after the last VEGF-SPECT scan and immunohistological (IHC) VEGF tumour expression was compared with In-111-bevacizumab tumour uptake.

Results: Nine patients were included. FOG-PET and CT detected both in total 12 nodal lesions which were all visualised by VEGF-SPECT. At baseline, In-111-bevacizumab tumour uptake varied 3-fold between and 1.6 +/- 0.1-fold within patients. After a therapeutic dose of bevacizumab there was a 21 +/- 4% reduction in In-111-bevacizumab uptake. The In-111-bevacizumab tumour uptake in the second series positively correlated with the VEGF-A expression in the resected tumour lesions.

Conclusion: VEGF-SPECT could visualise all known melanoma lesions. A single dose of bevacizumab slightly lowered In-111-bevacizumab uptake. Future studies should elucidate the role of VEGF-SPECT in the selection of patients and the individual dosing of bevacizumab treatment. (C) 2011 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1595-1602
Number of pages8
JournalEuropean Journal of Cancer
Volume47
Issue number10
DOIs
Publication statusPublished - Jul-2011

Keywords

  • VEGF
  • Melanoma
  • Bevacizumab
  • Imaging
  • SPECT
  • Biomarker
  • ENDOTHELIAL GROWTH-FACTOR
  • POSITRON-EMISSION-TOMOGRAPHY
  • METASTATIC BREAST-CANCER
  • RADIOLABELED BEVACIZUMAB
  • MALIGNANT-MELANOMA
  • ANGIOGENIC FACTORS
  • ANTIBODY BEVACIZUMAB
  • WEEKLY PACLITAXEL
  • PHASE-2 TRIAL
  • A EXPRESSION

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