Page 160 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 8
ABSTRACT
Purpose: Ideally, monoclonal antibodies provide selective treatment by targeting the tumor, without affecting normal tissues. Therefore antibody imaging is of interest, preferably in early stages of drug development. However, the imaging signal consists of specific, as well as non-specific uptake. The aim of this study was to assess specific, e.g. target-mediated uptake in normal tissues, with immuno- PET in a phase I dose escalation study, using the anti-CD44 antibody RG7356 as example.
Methods: Thirteen patients with advanced CD44-expressing solid tumors were included in this imaging sub-study of a phase I dose escalation clinical trial. 37 MBq of 89Zirconium-labeled RG7356 (1 mg) was administered after a variable dose of unlabeled RG7356 (0 to 675 mg). Tracer uptake in normal tissues (liver, spleen, kidney, lung, bone marrow, brain and blood pool) was used to calculate the area under the time antibody concentration curve (AUC) and expressed as tissue-to-blood AUC ratio’s.
Results: Within the dose range of 1 to 450 mg, tissue-to-blood AUC ratios decreased from 10.6 to 0.75 ± 0.16 for the spleen, 7.5 to 0.86 ± 0.18 for the liver, 3.6 to 0.48 ± 0.13 for bone marrow, 0.69 to 0.26 ± 0.1 for lung and 1.29 to 0.56 ± 0.14 for the kidney, indicating dose-dependent uptake. In all patients receiving ≥ 450 mg (n=7), tumor uptake of the antibody was observed.
Conclusion: This study demonstrates how immuno-PET in a dose-escalation study provides a non-invasive technique to quantify dose-dependent uptake in normal tissues, indicating specific, target-mediated uptake.
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