Page 39 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Dosimetry of immuno-PET with 89Zr-cmAb U36
However, with modern PET/CT scanners, 89Zr-immuno-PET data can be collected along with a structural CT image in one scanning session. The aligned CT data can then be used for a more accurate and automated VOI definition.
The mean radiation dose for patients in this study was about 40 mSv, which 2 is high and will limit repeated application of 89Zr-immuno-PET. However, the introduction of the new generation PET/CT scanners will also make that better
quality immuno-PET images can be obtained with the use of less 89Zr radioactivity
dose. This can be concluded from preliminary PET/CT studies in which 37 MBq 89Zr-trastuzumab was used for HER2 immuno-PET imaging in breast cancer patients (15). Using 89Zr-cmAb U36 in combination with these scanners would mean an effective dose of about 20 mSv for a whole body scan. Theoretically, shorter lived residualizing positron emitters like 64Cu (t1⁄2 = 12.7 h) and 86Y (t1⁄2 = 14.7 h) might give less dose exposure, although, clinical experience with these positron emitters is very limited. In a study of Cutler et al., immuno-PET with 370 MBq 64Cu-labeled intact mAb 1A3 was evaluated for detection of colorectal cancer with a Siemens/CTI ECAT EXACT PET scanner as was also used in the present study (31,32). The average whole body dose for these patients was 11.1 mSv. However, due to the short half-life of 64Cu, most of the patients had to be imaged within 24 h p.i. to obtain good quality images. As shown in Figure 1A, for cmAb U36 delineation of tumors is much better at later time points (72 and 144 h), and therefore, the use of 64Cu might be a less suitable alternative. For immuno-PET evaluation of antibody fragments, however, 64Cu as well as 86Y might be suitable candidates.
CONCLUSION
In the present study we evaluated the use of immuno-PET with 89Zr-labeled-cmAb U36 in HNSCC patients regarding safety, biodistribution, radiation dose, and the potential for quantification. 89Zr-cmAb U36 was found to be safe and well tolerated in all subjects. Uptake of radioactivity in heart, lungs, liver, kidneys, and spleen was decreasing over time, while increased uptake was only seen at tumor sites and in the thyroid of some of the patients. Quantitative analysis, comparing PET derived bloodpool activity and sampled blood activity, showed good agreement except for the patients with a body weight above 100 kg. Also a good agreement was found for assessment of antibody uptake in tumors. The mean effective dose
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