Page 127 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Interobserver reproducibility of 89Zr-immuno-PET
lymphoma ((6); Dutch Trial Register NTR 3392), 89Zr-cetuximab in patients with colorectal cancer ((5); NCT01691391) and 89Zr-trastuzumab in patients with breast cancer ((7); NCT01691391). These studies had been approved by the ethics committees (Medisch Ethische Toetsingscommissie VUmc and Medisch Ethische Toetsingscommissie UMC Groningen) and all subjects signed an informed consent. Data acquisition and visual assessment of tumor uptake was done locally: from the first two studies performed at the VUmc all subjects with visible tumor uptake were included, from the last study performed at the UMCG seven subjects were selected randomly. Scan data at 1 hour (D0), 72 hours (D3) and 144 hours (D6) post injection (p.i.) for 89Zr labeled rituximab and cetuximab and at 96 hours (D4) p.i. for 89Zr-trastuzumab were included. See Table 1 for patient characteristics and 89Zr-immuno-PET scan details. 89Zr-rituximab and 89Zr-cetuximab PET scans were performed on a Philips Gemini TF-64 or Ingenuity TF-128 PET-CT scanner (Philips Healthcare, the Netherlands). A Siemens Biograph mCT64 PET-CT scanner (Siemens Healthcare, the Netherlands) was used for the 89Zr-trastuzumab- PET scans.
VOI delineation 6 All immuno-PET scans were acquired and reconstructed to conform to recommendations for multicenter harmonization of 89Zr-immuno-PET (8). Visual
assessment of immuno-PET scans was performed by an experienced nuclear
medicine physician (OSH for 89Zr-rituximab and 89Zr-cetuximab, AHB for 89Zr- trastuzumab). Tumor uptake was defined as focal uptake exceeding local background. For visually positive tumor lesions, a screenshot indicating tumor localization on immuno-PET was obtained for tumor uptake quantification. Quantitative assessment of tumor uptake for all lesions was independently performed by 3 observers (1 data analyst (SP), 2 physician-researchers (FB, YJ)). Tumor delineation for all VOI was performed using the ACCURATE software tool (developed in IDL version 8.4 (Harris Geospatial Solutions, Bloomfield, USA)) [9].
The observers recorded the analysis time per tumor lesion and VOI delineation method.
Manual tumor delineation on immuno-PET. The observers manually delineated tumor VOI on the immuno-PET scans (attenuation corrected image), using the low dose CT for anatomical reference (Figure 2a). Adjustment of the following
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