Page 69 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Initial clinical trials with 89Zr-immuno-PET in oncology
89Zr-labeled anti-CD44v6 mAb in head and neck cancer
89Zr-immuno-PET is considered to be an attractive imaging technique for whole body tumor detection, due to the combined sensitivity of PET and the specificity of the mAb. Assessment of biodistribution of the mAb to confirm specificity of the mAb is particularly of interest to qualify the suitability of the mAb for therapy.
Börjesson et al. reported on the first clinical 89Zr-immuno-PET study ever
(11). In this study, twenty pre-operative patients with head and neck squamous
cell carcinoma (HNSCC) were included. Immuno-PET with 89Zr-labeled chimeric
mAb U36 (cmAb U36) was investigated in order to improve tumor detection of
HNSCC, especially in lymph nodes, and to assess the targeting potential of the 4 mAb for therapy. cmAb U36 targets the v6 region of CD44 (cluster of differentiation;
CD44v6). Homogeneous expression of CD44v6 has been observed in several malignancies, including HNSCC, lung, skin, esophagus, and cervix carcinoma.
Expression of CD44v6 has also been reported in normal epithelial tissues, such as
skin, breast, and prostate myoepithelium, and bronchial epithelium.
Administration of 74 megabecquerel (MBq) 89Zr-mAb U36 (10 mg) appeared to be safe, as no adverse reactions were observed. A human anti-chimeric antibody response was reported in 2 patients, which was not directed to the chelate, but to the protein part of the conjugate. 89Zr-immuno-PET scans were visually scored. All primary tumors were detected and 89Zr-immuno-PET performed equally to computed tomography (CT)/magnetic resonance imaging (MRI) for detection of lymph node metastasis. Although biopsies were obtained in this study to confirm tumor localization, immunohistochemistry for CD44v6 was not performed, as in literature > 96% of HNSCC show CD44v6 expression by at least 50% of the cells. This study shows that immuno-PET with 89Zr-cmAb U36 can be used as an imaging modality for tumor detection. However, traditional imaging techniques as 18F-fluoro-deoxy-glucose(FDG)-PET and sentinel node procedures for assessment of lymph node status remain standard of care for tumor detection in HNSCC patients, as the added value of immuno-PET with 89Zr-cmAb U36 has not been demonstrated.
In a separate publication, biodistribution, radiation dose and quantification of 89Zr-labeled cmAb U36 were reported for the same patient cohort (12). 89Zr-cmAb U36 in blood pool, lungs, liver, kidneys and spleen decreased over time. Increasing uptake of 89Zr-cmAb U36 over time was seen only at tumor sites and in the thyroid of some patients (suggesting expression of CD44v6 in thyroid of these patients). Although expression of CD44v6 in normal epithelial tissue has been described, no
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