Page 148 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

Chapter 7
in case of focal uptake exceeding local background. Immuno-PET scans were classified as positive (moderate or intense, at the D6 scan) or negative for tumor uptake of 89Zr-rituximab in the biopsied tumor lesion. Thereafter, the immuno- PET scans were compared with the 18F-FDG-PET scans to confirm tumor localization. Tumor volumes of interest (VOIs) were manually delineated on immuno-PET scans at D3 and D6, using a semi-automatic in-house software tool. Peak (i.e. average value of a 12mm sphere positioned within the VOI so as to obtain the highest value) and mean activity concentrations (ACpeak and ACmean, respectively) were derived per tumor VOI. For ACmean standard deviations (SD) were derived per VOI. Blood pool VOIs were delineated using a fixed size VOI of the aortic arch (volume of 1.6 mL), on the ldCT and imported to the PET images. ACmean was derived per blood pool VOI. Standardized uptake values (SUVpeak and SUVmean ± SD, respectively) were calculated for tumor lesions, and decay corrected to the time of injection. Tumor to blood ratio’s (T/B) for tumor lesions were calculated as tumor AC on D6 divided by image derived blood pool AC on D6. To assess tumor uptake over time, SUVpeak D6/D3 ratios were calculated.
Patients were ranked based on the level of CD20 expression in order to correlate biopsy results to tumor uptake of 89Zr-rituximab, defined on PET images. Spearman’s rank correlation coefficient (rs) as well as the two-tailed p-value were calculated to explore the relation between tumor uptake of 89Zr-rituximab, measured as SUVpeak, and the level of CD20 expression in the biopsied lesions. Statistical tests were performed using SPSS Statistics Version 22 (IBM software).
RESULTS
Six patients with a primary diagnosis of CD20-positive DLBCL, with refractory or relapsed disease after first line treatment with R-CHOP, were included. Patient characteristics are summarized in Table 1.
Patient 2 and 6 had primary refractory disease, with a partial remission (PR) after R-CHOP. The other patients had relapsed disease, of whom two patients (1 and 3) had an early relapse within 1 year after R-CHOP. In all patients 18F-FDG- PET scans were obtained for staging, before start of second line treatment. All patients were subsequently treated in second line with rituximab combined with high dose cytarabine, cisplatin and dexamethasone (R-DHAP).
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