Page 201 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

(accuracy 93%) and in 19 of 25 sides (accuracy 76%). Two false-positive findings (two levels) were obtained with 89Zr-immuno-PET, without explanation. Seven tumor-involved lymph node levels were missed by 89Zr-immuno-PET. These tumor-involved lymph nodes were relatively small (<1x 1.5cm), and contained just a small proportion of tumor tissue (~50% tumor infiltration). For CT/MRI, accuracy per level and per sided were 90% (109/121) and 80% (20/25), respectively. Six out of 7 tumor-involved lymph node levels that had been missed by 89Zr- immuno-PET, were also missed by CT and/or MRI. In conclusion, these results indicate that the diagnostic imaging performance of 89Zr-immuno-PET was similar to CT/MRI for the detection of HNSCC lymph node metastases.
In daily clinical practice, CT and MRI are already established diagnostic imaging modalities. This study shows that visual detection of tumor uptake of 89Zr-cmAb U36, a novel imaging technique, is feasible. Next to diagnostic implications, these achievements might open avenues for guiding the development and application of therapeutic antibodies.
Tumor uptake and blood pool activity can be quantified with 89Zr-immuno-PET
In Chapter 2, feasibility of quantification with immuno-PET with 89Zr-cmAb U36 is described. PET-derived quantification of radioactivity concentrations in the left ventricle of the heart showed good agreement with radioactivity concentrations measured in venous blood samples (difference equals 0.2% ± 16.7% [mean ± SD]), except for heavyweight patients (>100kg). For tumors, good agreement was found between PET-derived quantification at 6 days p.i. and measurement of radioactivity concentrations in surgical biopsies obtained at 7 days p.i., with slightly lower values for PET (mean deviation -8.4% ± 34.5%).
Clinical 89Zr-immuno-PET studies in oncology provide relevant and sustainable results
In Chapter 4, we provide a review summarizing the results from the first 15 clinical trials with 89Zr-immuno-PET in oncology published between 2006 and 2016. These trials have contributed towards the development of 89Zr-immuno-PET as an imaging biomarker by showing correlation between uptake of 89Zr-labeled mAbs on PET and target expression levels in biopsies.
The ZEPHIR study is an example how 89Zr-immuno-PET, combined with early response assessment by 18F-FDG-PET, can be used to predict response to antibody-based therapy, in this case with the antibody-drug conjugate,
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Summary and discussion
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