Page 166 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 8
89Zr-RG7356 PET: biodistribution
Overall, visual assessment of PET images showed mainly blood pool activity of 89Zr-labeled-RG7356 at 1 hour post injection (p.i.), decreasing over time (Figure 2A). Differences in biodistribution of 89Zr-labeled-RG7356 were observed for patients in the different dose cohorts. Intense tracer uptake in the spleen, liver and bone marrow was visualized for the lowest dose cohorts (1 and 100 mg), decreasing with increasing antibody doses (Figure 2B).
The blood pool activity concentration of 89Zr-labeled-RG7356, expressed as standardized uptake value (SUV) over time is shown in Figure 3A. This graph displays only the measured activity of the radioactive tracer. In Figure 3B, derived absolute antibody concentrations in blood pool, which represent the total amount of antibody (labeled + unlabeled dose) are shown. The area under the curve (AUC) of this time antibody concentration curve is shown as a function of the administered antibody dose in Figure 3C. Dose independent uptake would result in a linear relationship of AUC with antibody dose. Figure 3C does, overall, show this linear relationship. The 100 mg datapoint, however, has a measured AUC lower than expected based on this linear trend.
Tissue-to-blood AUC ratios are presented as a function of administered antibody dose in Figure 4. For the brain, the tissue-to-blood AUC ratio was constant (0.07 ± 0.01) and independent of administered antibody dose. All other tissue-to-blood AUC ratios (spleen, liver, bone marrow, kidney and lung) were dependent of the antibody dose administered.
For the lowest dose cohorts (1 and 100 mg), relative high tissue-to-blood AUC ratios were observed. The spleen showed the highest tissue-to-blood AUC ratio for the 1 mg dose cohort (10.6), followed by liver (7.5), bone marrow (3.6), kidney (1.3), lung (0.7) and brain (0.08). For liver, spleen and kidney, a constant tissue-to blood AUC ratio was reached for doses ≥ 450 mg, for the lung at doses ≥ 200 mg. For the 675 mg dose cohort, the liver showed the highest tissue-to-blood AUC ratio of 0.85 ± 0.08, followed by spleen (0.72 ± 0.09), kidney (0.59 ± 0.08), bone marrow (0.40 ± 0.04), lung (0.27 ± 0.03) and brain (0.07 ± 0.02).
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