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

Abstract

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 ( 89 Zr) 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 89 Zr-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 89 Zr 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 18 F-fluoro-2-deoxy-D-glucose. Immuno-PETscans 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-PETdetected all primary tumors (n = 17) as well as lymph node metastases in 18 of 25 positive levels (sensitivity 72%) and in 11of 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 tumorinvolved neck levels and sides, immuno-PETand 18 F-fluoro-2-deoxy-D-glucose PETgave comparable diagnostic results. Conclusion: In this study, immuno-PET with 89 Zr-cmAb U36 performed at least as good as CT/MRI for detection of HNSCC lymph node metastases.

Tissue Distribution Studies of Protein Therapeutics Using Molecular Probes: Molecular Imaging

“…It is already proven with numerous antibodies (39,(70)(71)(72)(73)(74) and other proteins (75,76) through the efforts of groups in The Netherlands where it has been developed in both preclinical and, with good manufacturing practices (GMP) production for tracer production and validation, in clinical settings. Although Zr-89 does have an extraneous high-energy gamma ray (909 keV), the image quality is good and the overall radiation burden is well tolerated (77).…”

CD44 in hematological neoplasias

“…This in turn might indicate a promising role in treatment of hematological malignancies. Besides of the therapeutic effect also diagnostic use of CD44v6 antibodies is shown by successful detection of HNSCC lymph node metastases via immuno-PET by 89 ZrcmAb U36 [139,138].…”

A Versatile Bifunctional Chelate for Radiolabeling Humanized Anti-CEA Antibody with In-111 and Cu-64 at Either Thiol or Amino Groups: PET Imaging Of CEA-Positive Tumors with Whole Antibodies

“…86 Zr is attractive in terms of its long half-life and good spatial imaging, but has a potential problem with a 909 keV gamma emission. Appropriate BFCs for this metal ion have only recently been desctibed (11). 64 Cu was chosen for the studies reported here based on its wide availability, good spatial resolution, and relatively short half-life, limiting its potential imaging dose to patients.…”