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Zr-89-Bevacizumab PET Visualizes Disease Manifestations in Patients with von Hippel-Lindau Disease

Oosting, S. F., van Asselt, S. J., Brouwers, A. H., Bongaerts, A. H. H., Steinberg, J. D. J., de Jong, J., Lub-de Hooge, M. N., Horst-Schrivers, van der, A. N. A., Walenkamp, A. M. E., Hoving, E. W., Sluiter, W. J., Zonnenberg, B. A., de Vries, E. G. E. & Links, T. P., 1-Aug-2016, In : Journal of Nuclear Medicine. 57, 8, p. 1244-1250 7 p.

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  • Zr-89-Bevacizumab PET Visualizes Disease Manifestations in Patients with von Hippel-Lindau Disease

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DOI

Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable, and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor A (VEGF-A) produced locally is supposed to play an important role in development of disease manifestations and is a target for antiangiogenic therapy with the monoclonal antibody bevacizumab. We aimed to assess whether VHL manifestations can be visualized with Zr-89-bevacizumab PET and to explore whether Zr-89-bevacizumab PET can differentiate progressive from nonprogressive lesions. Methods: VHL patients with at least 1 measurable hemangioblastoma were eligible. Zr-89-bevacizumab (37 MBq) was administered intravenously 4 d before the scan. Maximum standardized uptake values were calculated. PET scans were fused with routine MRI of the central nervous system and abdominal MRI or CT. Progressive lesions were defined as new lesions, lesions that became symptomatic, and lesions >= 10 mm that increased >= 10% and >= 4 mm on repeated anatomic imaging within 12 mo. Results: Twenty-two patients were enrolled. At baseline, anatomic imaging showed 311 lesions. Zr-89-bevacizumab PET visualized 59 VHL manifestations, 0-17 per patient. The median of maximum standardized uptake values was 8.5 (range, 1.3-35.8). The detection rate for lesions >= 10 mm was 30.8%. Seven additional hotspots without substrate on baseline anatomic imaging were found; 2 were also detected with anatomic imaging during follow-up. Nine of 25 progressive lesions were visible on PET and 27 of 175 nonprogressive lesions, corresponding to a positive predictive value of 25% and a negative predictive value of 90%. SUVmax was similar in progressive and nonprogressive lesions (median, 4.8; range, 0.9-8.9 vs. median, 6.7; range, 1.3-35.8, P = 0.14). Conclusion: VHL manifestations can be visualized with Zr-89-bevacizumab PET with a striking heterogeneity in tracer accumulation. Zr-89-bevacizumab uptake does not predict progression within 12 mo. In one third of the lesions, the drug target VEGF is available and accessible. Zr-89-bevacizumab PET might offer a tool to select VHL patients for anti-VEGF therapy.

Original languageEnglish
Pages (from-to)1244-1250
Number of pages7
JournalJournal of Nuclear Medicine
Volume57
Issue number8
Publication statusPublished - 1-Aug-2016

    Keywords

  • von Hippel-Lindau disease, hemangioblastoma, positron emission tomography, vascular endothelial growth factor, bevacizumab, ENDOTHELIAL GROWTH-FACTOR, RENAL-CELL CARCINOMA, CENTRAL-NERVOUS-SYSTEM, TUMOR-SUPPRESSOR GENE, ANTIANGIOGENIC TREATMENT, RETINAL HEMANGIOBLASTOMAS, NATURAL-HISTORY, EXPRESSION, THERAPY, SUNITINIB

ID: 32386101