Page 37 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Dosimetry of immuno-PET with 89Zr-cmAb U36
DISCUSSION
The purpose of this study was to assess the safety, and to evaluate the biodistribution,
the radiation dose, and the potential for quantification of immuno-PET with 89Zr- 2 labeled-chimeric mAb (cmAb) U36 in HNSCC patients. In this study, the tracer
was found to be safe and well tolerated. No adverse events occurred. A HACA
response was only seen in two patients, while none of the antibody responses was
directed to the chelate. In all normal organs, the uptake of radioactivity decreased
in time. Only in the tumor and in a few patients in the thyroid, uptake increased
in time, suggesting specific uptake of 89Zr-cmAb U36. Such variable and sometimes
high thyroid uptake was previously observed in head and neck cancer patients
who had been injected with 99mTc-cmAb U36 (16). This might indicate that in
some individuals CD44v6 is expressed in the thyroid.
Furthermore, the advantage of the more detailed images obtained with 89Zr-immuno-PET is the possibility of non-invasive quantification. In the majority of the images the visual quality was acceptable for defining ROI’s, but there was a variation between images of different patients and in some images the delineation of organs and tumor was suboptimal. Nevertheless, quantification results seem plausible. The 89Zr calibration procedure indicated that the quantitative accuracy of the scanner was not compromised by the presence of 909 keV gamma photons emitted from 89Zr and due to emission spillover into the transmission scans. In fact, the procedure was repeated for activity concentrations of about 17 kBq/cc (111 MBq in a phantom of 6283 ml) showing that quantitative accuracy was not affected at higher count rates as well. Although the 909 keV photons could have resulted in increased dead time and randoms fraction, the 89Zr activity in the field of view is much lower than usually applied for e.g. FDG studies (up to 370 MBq FDG for patients and about 70 MBq FDG in a 6 L phantom for calibrations). Moreover, the 511 keV photon flux from 89Zr is much lower than that seen in FDG studies due to lower positron emission abundance compared with 18F. Another effect that could hamper quantification might be emission spillover into the transmission scan. However, emission spillover into the transmission scan is minimized in two ways. First, transmission scans are based on coincidence counting of the 511 keV photons emitted by the 68Ge transmission rod sources, thereby reducing the detection of non-coincident emitted photons (although these still result in increased randoms fraction). Second, during transmission scanning a “rod windowing” technique is applied (26). Rod windowing discards all detected
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