Page 61 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer
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                                Immuno-PET with 89Zr-cMab U36 in head and neck cancer
metastases. Because surgical management is reserved for patients with locoregional
disease, the presence of distant metastases is critical and may significantly influence
treatment. Recent studies have shown that there is a role for FDG-PET in the
detection of occult distant metastases (20). It can be anticipated, however, that the
use of immuno-PET with 89Zr-labeled MAbs might add another dimension to the
detection of distant metastases, especially when the same MAb is used for systemic
therapy. Within such a strategy, immuno-PET might play a dual role: tumor 3 detection as well as treatment planning.
MAbs are gaining momentum for the use in tumor-selective systemic therapy, also for treatment of head and neck cancer. Presently, 17 MAbs (all intact IgGs) have been approved by the Food and Drug Administration for therapy, most of them for systemic treatment of cancer. Of the approved MAbs, cetuximab (directed against the epidermal growth factor receptor) and bevacizumab (directed against the vascular endothelial growth factor) are also used in strategies for treatment of head and neck cancer. In addition, several other MAbs are under evaluation for therapy of head and neck cancer, such as the radiolabeled MAbs U36 (4,5) and L19. The latter MAb is directed against the ED-B domain of fibronectin, and capable of selective targeting of tumor neovasculature (21-23). Data presented in this initial clinical feasibility study justify further exploration of 89Zr-immuno-PET as an imaging tool for the selection of high-potential candidate MAbs for therapy as well as of patients most likely to benefit from (expensive) MAb treatment.
ACKNOWLEDGMENTS
We thank the staff of BV Cyclotron (VU University) for supply of 89Zr, Dr. Jan H. Rector (Solid State Physics, VU University) for sputtering 89Y on copper supports, Dr. Gerard W.M. Visser and Dr. Iris Verel for advice on radiochemistry, Ing. Henri N.J.M. Greuter for pharmacokinetic determinations, Dr. Bram J. Wilhelm for pharmacokinetic modeling, Ing. Marijke Stigter for human antichimeric antibody analyses, Dr. Jan C. de Munck for image fusion, Dr. D. Joop Kuik for advice on statistics, and Dr. Manfred van der Vlies for supervision of radiation safety issues.
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