Page 48 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 3
100.3 hours). Of these isotopes, 89Zr can be obtained with high yield, high radionuclide purity, and low production costs (9). Moreover, 89Zr has ideal characteristics for optimal image quality and accurate quantification. Stable coupling of 89Zr to MAbs was accomplished using the succinylated chelate desferrioxamine B (desferal) (9). The suitability of such conjugates, 89Zr-labeled cMAb U36 included, for detection of millimeter-sized tumors was shown in HNSCC xenograft-bearing nude mice (10). In addition, the potential of PET for quantification of 89Zr-labeled MAbs was shown in these studies (10).
Based on aforementioned encouraging preclinical results, we hypothesized that PET with 89Zr-labeled MAb U36 might be better suited for detection of lymph node metastases in HNSCC patients than previously tested single-photon emission computerized tomography (SPECT) approaches with MAb U36. To the best of our knowledge, the long-lived positron emitter 89Zr has never been tested in a clinical setting before. In the present study, PET with 89Zr-labeled MAb U36 was evaluated for its safety and preliminary diagnostic accuracy in patients with proven HNSCC and clinically at high risk of having lymph node metastases.
MATERIALS AND METHODS
Patient Study
Twenty patients, who were at high risk of having neck lymph node metastasis from a proven HNSCC and who were planned to undergo neck dissection with or without resection of the primary tumor, participated in this study. Decision about the need for neck dissection, and the type of neck dissection, was based on primary tumor site and tumor stage as found by conventional clinical and diagnostic examinations. Immuno-PET did not influence this decision. Confirmation of CD44v6 expression by biopsy was not required, as > 96% of tumors show CD44v6 expression by at least 50% of the cells (11). The primary tumor and the status of neck lymph nodes were classified according to the tumor-node-metastasis system of the International Union Against Cancer (12). Patient and tumor characteristics are given in Table 1.
Prior and up to 6 weeks after administration of radiolabeled cMAb U36, routine laboratory analyses were done, including complete blood cell counts, serum electrolytes, urine sediment, liver enzymes, and renal and thyroid functions. Vital signs were recorded before and up to 3 hours after injection.
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