Page 54 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 3
additional diagnostic value by identification of patients with enlarged lymph nodes (4-11 mm) eligible for ultrasound-guided fine-needle aspiration cytology, (b) clinical 89Zr-immuno-PET was used for the first time ever, and therefore it was not known beforehand whether all parameters were optimal for tumor detection, e.g., injected 89Zr dose and image acquisition, reconstruction, and evaluation. In addition, procedures for 89Zr quantification are under development, and were not available for the present evaluation.
RESULTS
Neither adverse reactions nor significant changes in blood and urine values were observed, which could be related to the injection of the antibody. Patient 9 and 10 developed a human antichimeric antibody response, and elevated titers were found at 1 and 6 weeks post injection, whether or not cMAb U36 IgG or 89Zr-N- sucDf-cMAb U36 was used in the ELISA. These data indicate that the response was directed to the protein part of the conjugate and not to the N-succinyldesferrioxamine B chelate attached to the cMAb. None of the samples showed exclusive positivity in the 89Zr-N-sucDf-cMAb U36 ELISA, indicating that immunogenicity of the chelate is low.
Whole body images obtained directly after administration of 89Zr-cMAb U36 showed mainly blood-pool activity with delineation of nose, heart, lungs, liver, spleen, and kidneys. Uptake of radioactivity in these organs decreased over time, whereas increased uptake was seen only at tumor sites. No selective accumulation at nontumor sites was observed. Representative whole body scans are shown in Figure 1. In the 20 patients studied, all 17 tumors at the primary site were visualized by immuno-PET, including one unknown primary tumor (patient 2). From the 20 patients, lymph nodes present in 25 neck dissections in 121 levels were examined histopathologically for tumor involvement. HNSCC metastases were found in 25 levels in 15 sides. There was no evidence for presence of distant metastases. Representative immuno-PET images of patients with primary tumor and lymph node involvement (patients 16 and 19) are shown in Figures 2 and 3.
52