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

Initial clinical trials with 89Zr-immuno-PET in oncology
For patients with preserved circulating CD20-positive B-cells (n = 2) without a preload of unlabeled rituximab, an increase in whole-body radiation dose of 59% and 87% was observed mainly due to increased uptake in the spleen, see Figure 4. The effective dose of 89Zr-rituximab was 0.50 milliSievert (mSv)/MBq without a preload and 0.41 mSv/MBq with a preload.
These results suggest that administration of the standard preload of
unlabeled rituximab impairs tumor targeting of 89Zr-rituximab in patients
with B-cell depletion, due to previous treatment with rituximab. These data
suggest that common practice of preloading with unlabeled rituximab before
RIT should be re-evaluated and reconsidered. 4
Figure 4. 89Zr-rituximab-PET images obtained 6 days after injection (A) Patient 2 without B cell depletion, anterior view
(B) Patient 3 with B cell depletion, posterior view
Reprinted with permission from “Muylle, K., Flamen, P., Vugts, D.J., Guiot, T., Ghanem, G., Meuleman, N., et al. (2015). Tumour targeting and radiation dose of radioimmunotherapy with 90Y-rituximab in CD20+ B-cell lymphoma as predicted by 89Zr-rituximab immuno-PET: impact of preloading with unlabelled rituximab. Eur. J. Nucl. Med. Mol. Imaging. 42, 1304-1314. doi: 10.1007/s00259-015-3025-6”
CONCLUSIONS AND FUTURE DIRECTIONS
In clinical trials with 89Zr-immuno-PET, two requirements should be met in order to realize its full potential. One requirement is that the biodistribution of the 89Zr- mAb (imaging dose) should reflect the biodistribution of the drug during
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