title: 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.
abstract: 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.
authors: Department of Radiology, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511 Japan.
authors: Kohei
authors: K
authors: Hanaoka
authors: Division of Positron Emission Tomography, Institute of Advanced Clinical Medicine, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511 Japan.
authors: Makoto
authors: M
authors: Hosono
authors: Department of Hematology, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511 Japan.
authors: Yoichi
authors: Y
authors: Tatsumi
authors: Neurocognitive Disorders Center, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511 Japan.
authors: Kazunari
authors: K
authors: Ishii
authors: Department of Radiology, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511 Japan.
authors: Sung-Woon
authors: SW
authors: Im
authors: Division of Positron Emission Tomography, Institute of Advanced Clinical Medicine, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511 Japan.
authors: Norio
authors: N
authors: Tsuchiya
authors: Division of Positron Emission Tomography, Institute of Advanced Clinical Medicine, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511 Japan.
authors: Kenta
authors: K
authors: Sakaguchi
authors: Department of Hematology, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511 Japan.
authors: Itaru
authors: I
authors: Matsumura
keywords: FDG; Heterogeneity; Ibritumomab tiuxetan; PET/CT; Radioimmunotherapy; SPECT/CT