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89Zr-immuno-PET in a phase I trial
Figure 1. Immuno-PET signal components in a phase I dose escalation study. The tissue-to-blood ratio is shown as a function of administered antibody dose. For example target-antigen-mediated uptake is dose- dependent, while blood volume fraction, catabolism or elimination are dose-independent accumulation mechanisms.
MATERIALS AND METHODS
Patient population
Patients with advanced CD44-expressing solid tumors were included in a multicentre phase I clinical study with RG7356 (ClinicalTrials.gov Identifier NCT01358903) (10). As part of the screening procedure, tumor biopsies were
obtained and analysed centrally by Ventana Medical Systems Inc. (VSMI, Tucson, 8 AZ, USA), using clone SP37 as anti-CD44 primary antibody to assess tissue
quality, tumor content and CD44 expression by immunohistochemistry (IHC). Patients with a IHC score of ≥1+ for CD44-positivity on the pretreatment biopsy were included. For specific scoring criteria for CD44 expression in patient samples, see Supplemental Table 1. Study design as well as inclusion and exclusion criteria have been reported previously (5). This study was approved by the Medical Ethics Review Committee of the VU University Medical Center, Amsterdam, and performed in accordance with the Declaration of Helsinki. All study-related procedures were performed after patients gave their written informed consent. Patients enrolled in this phase I study at the VU University Medical Center were asked to participate in the exploratory imaging sub-study.
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