Heterogeneity of intratumoral (111)In-ibritumomab tiuxetan and (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 (111)In-ibritumomab tiuxetan (Zevalin®) and tumor accumulation of (18)F-fluoro-deoxyglucose (FDG) and compare them to the tumor response in B-cell non-Hodgkin’s lymphoma patients receiving (90)Y-ibritumomab tiuxetan (Zevalin®) therapy. METHODS: Sixteen patients with histologically confirmed non-Hodgkin’s B-cell lymphoma who underwent (90)Y-ibritumomab tiuxetan therapy along with (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 (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 (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 (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 (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 (111)In-ibritumomab tiuxetan demonstrated skewness of 0.58 ± 0.16 and 0.73 ± 0.24 (p < 0.05), kurtosis of 2.39 ± 0.32 and 2.78 ± 0.53 (p < 0.02), and AUC-CSH of 0.37 ± 0.04 and 0.34 ± 0.05 (p < 0.05) for responders and non-responders. CONCLUSIONS: Pretherapeutic FDG accumulation was predictive of the tumor response in (90)Y-ibritumomab tiuxetan therapy. The heterogeneity of the intratumoral distribution rather than the absolute level of (111)In-ibritumomab tiuxetan was correlated with the tumor response.