Heterogeneity of intratumoral ^sup 111^In-ibritumomab tiuxetan and ^sup 18^F-FDG distribution in association with therapeutic response in radioimmunotherapy for B-cell non-Hodgkin's lymphoma

Background The purpose of this study was to quantitatively evaluate the tumor accumulation and heterogeneity of ^sup 111^In-ibritumomab tiuxetan (Zevalin) and tumor accumulation of ^sup 18^F-fluoro-deoxyglucose (FDG) and compare them to the tumor response in B-cell non-Hodgkin's lymphoma patients receiving ^sup 90^Y-ibritumomab tiuxetan (Zevalin) therapy. Methods Sixteen patients with histologically confirmed non-Hodgkin's B-cell lymphoma who underwent ^sup 90^Y-ibritumomab tiuxetan therapy along with ^sup 111^In-ibritumomab tiuxetan single-photon emission computerized tomography (SPECT)/CT and FDG positron emission tomography (PET)/CT were enrolled in this retrospective study. On pretherapeutic FDG PET/CT images, the maximum standardized uptake value (SUVmax) was measured. On SPECT/CT images, a percentage of the injected dose per gram (%ID/g) and SUVmax of ^sup 111^In-ibritumomab tiuxetan were measured at 48 h after its administration. The skewness and kurtosis of the voxel distribution were calculated to evaluate the intratumoral heterogeneity of tumor accumulation. As another intratumoral heterogeneity index, cumulative SUV-volume histograms describing the percentage of the total tumor volume above the percentage thresholds of pretherapeutic FDG and ^sup 111^In-ibritumomab tiuxetan SUVmax (area under the curve of the cumulative SUV histograms (AUC-CSH)) were calculated. All lesions (n=42) were classified into responders and non-responders lesion-by-lesion on pre- and post-therapeutic CT images. Results A positive correlation was observed between the FDG SUVmax and accumulation of ^sup 111^In-ibritumomab tiuxetan in lesions. A significant difference in pretherapeutic FDG SUVmax was observed between responders and non-responders, while no significant difference in ^sup 111^In-ibritumomab tiuxetan SUVmax was observed between the two groups. In contrast, voxel distribution of FDG demonstrated no significant differences in the three heterogeneity indices between responders and non-responders, while ^sup 111^In-ibritumomab tiuxetan demonstrated skewness of 0.58±0.16 and 0.73±0.24 (p