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Performance of Immuno–Positron Emission Tomography with Zirconium-89-Labeled Chimeric Monoclonal Antibody U36 in the Detection of Lymph Node Metastases in Head and Neck Cancer Patients

Authors' Affiliations: Departments of ¹ Otolaryngology/Head and Neck Surgery, ² Nuclear Medicine and Positron Emission Tomography Research, ³ Radiology, and ⁴ Pathology, VU University Medical Center, Amsterdam, the Netherlands

Requests for reprints: Guus A.M.S. van Dongen, Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands. Phone 31-20-4440953; Fax: 31-20-4443688; E-mail: gams.vandongen{at}VUmc.nl.

Purpose: Immuno–positron emission tomography (PET), the combination of PET with monoclonal antibodies (mAb), is an attractive option to improve tumor detection and to guide mAb-based therapy. The long-lived positron emitter zirconium-89 (⁸⁹Zr) has ideal physical characteristics for immuno-PET with intact mAbs but has never been used in a clinical setting. In the present feasibility study, we aimed to evaluate the diagnostic imaging performance of immuno-PET with ⁸⁹Zr-labeled-chimeric mAb (cmAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC), who were at high risk of having neck lymph node metastases.

Experimental Design: Twenty HNSCC patients, scheduled to undergo neck dissection with or without resection of the primary tumor, received 75 MBq ⁸⁹Zr coupled to the anti-CD44v6 cmAb U36 (10 mg). All patients were examined by computed tomography (CT) and/or magnetic resonance imaging (MRI) and immuno-PET before surgery. Six patients also underwent PET with ¹⁸F-fluoro-2-deoxy-D-glucose. Immuno-PET scans were acquired up to 144 hours after injection. Diagnostic findings were recorded per neck side (left or right) as well as per lymph node level (six levels per side), and compared with histopathologic outcome. For this purpose, the CT/MRI scores were combined and the best of both scores was used for analysis.

Results: Immuno-PET detected all primary tumors (n = 17) as well as lymph node metastases in 18 of 25 positive levels (sensitivity 72%) and in 11 of 15 positive sides (sensitivity 73%). Interpretation of immuno-PET was correct in 112 of 121 operated levels (accuracy 93%) and in 19 of 25 operated sides (accuracy 76%). For CT/MRI, sensitivities of 60% and 73% and accuracies of 90% and 80% were found per level and side, respectively. In the six patients with seven tumor-involved neck levels and sides, immuno-PET and ¹⁸F-fluoro-2-deoxy-D-glucose PET gave comparable diagnostic results.

Conclusion: In this study, immuno-PET with ⁸⁹Zr-cmAb U36 performed at least as good as CT/MRI for detection of HNSCC lymph node metastases.

Commentary

Potential of Immuno–Positron Emission Tomography for Tumor Imaging and Immunotherapy Planning

Michael R. Zalutsky
Clin. Cancer Res. 2006 12: 1958-1960. [Full Text] [PDF]

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