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                                89Zr-immuno-PET in a phase I trial Table 2 Tumor uptake of 89Zr-RG7356 and RG7356 at 96 h p.i..
Patient Dose cohort Visual Localisation SUVpeak AUC Tumor to blood (mg) assessment (mg·h/mL) AUC ratio
11-----
  2 100 -
3 100 +
4 100 -
5 200 -
6 200 -
7 450 +
8 450 +
9 450 +
10 450 +
11 450 +
12 675 +
13 675 +
- = no visible tumor uptake
*NA=not available (diffuse localization)
-
Lung (diffuse)
-
-
-
Brain L Lung R
Skull L
Upper neck L Lower neck L Supraclavicular R Mediastinal
Lung L
Lung R1
Lung R2
Lung L Lung R Rectum
Lung L Lung R
Mastoid L
Sigmoid L
Pelvic R Sacrum
- - -
NA* NA* -
- - -
- - -
- - -
1.8 0.35 0.09 8.4 2.06 0.55
3.3 1.41 0.43 3.5 1.62 0.49 2.8 1.43 0.43 3.1 1.67 0.50 4.8 2.37 0.72 2.2 1.29 0.39 2.1 1.06 0.32 4.3 1.75 0.53
1.8 0.89 0.32 2.2 0.99 0.36 5.6 1.75 0.64
4.6 1.47 0.56 3.9 1.41 0.53
4.5 1.81 0.42 4.9 2.55 0.59
6.5 3.83 0.73 8.1 3.29 0.63
 DISCUSSION 8
In this study, we assessed dose-dependent and dose-independent uptake of the 89Zr-labeled anti-CD44 antibody RG7356 in normal tissues to identify specific, e.g. target-mediated uptake on immuno-PET in a dose-escalation phase 1 study.
Both dose-dependent and dose-independent uptake was observed, reflecting specific as well as non-specific uptake of RG7356. For tissues without antigen expression, a linear increase in antibody concentrations can be expected for increasing antibody doses, driven by perfusion and blood volume of the tissue. However, our results suggest a mechanism that extracts antibody from the blood pool to tissues, in addition to the non-specific uptake mechanisms (Figure 3C).
Therefore, tissue-to-blood AUC ratios were used to evaluate dose- dependent uptake of RG7356 for the following tissues: liver, spleen, bone marrow,
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