Page 199 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

SUMMARY AND DISCUSSION
There is an urgent need for reliable biomarkers to increase efficacy and reduce unnecessary toxicity and costs of antibody-based therapy in cancer. Antibody imaging using positron emission tomography (PET) with 89-Zirconium (89Zr)- labeled mAbs provides a potential imaging biomarker by assessment of target engagement of therapeutic mAbs.
The aim of this thesis was to develop 89Zr-immuno-PET as a clinical tool to guide antibody-based therapy. Feasibility, technical and biological validation of 89Zr-immuno-PET were investigated as essential steps towards application in drug development and routine clinical practice.
Part I Feasibility of 89Zr-immuno-PET
89Zr-labeled mAbs are safe to administer
Chapter 2 describes the first clinical 89Zr-immuno-PET study. This study was performed in twenty patients with squamous cell carcinoma of the head and neck (HNSCC). Patients were at high risk of having neck lymph node metastases and therefore scheduled to undergo neck dissection (with or without resection of the primary tumor). All patients received 75 MBq of 89Zr-labeled chimeric monoclonal antibody (cmAb) U36 (10 mg) and immuno-PET scans were obtained up to 6 days post injection (p.i.).
Chapter 2 describes the safety of administration of 89Zr-cmAb U36. The procedure was well tolerated in all patients; no serious or drug-related adverse events were reported. Two patients developed a human-anti-chimeric antigen (HACA) response, related to the protein part of the 89Zr-labeled mAbconjugate, not to the chelate.
Administration of 89Zr-labeled mAbs was also well tolerated in the other clinical studies described in this thesis. No adverse events related to the radiotracer were reported for 89Zr-rituximab in patients with diffuse large B cell lymphoma (Chapter 7) and 89Zr-antiCD44 in patients with CD44-expressing solid tumors (Chapter 8). In addition, the first 15 clinical trials with 89Zr-immuno-PET in oncology (published between 2006 and 2016) showed no safety issues (Chapter 4).
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Summary and discussion
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