PurposePositron emission tomography (PET) with 89Zr-ibritumomab tiuxetan can be used to monitor biodistribution of 90Y-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of 90Y-ibritumomab tiuxetan in humans on the basis of 89Zr-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of 90Y-ibritumomab tiuxetan influences biodistribution of 89Zr-ibritumomab tiuxetan and whether pre-therapy scout scans with 89Zr-ibritumomab tiuxetan can be used to predict biodistribution of 90Y-ibritumomab tiuxetan and the dose-limiting organ during therapy.MethodsSeven patients with relapsed B-cell non-Hodgkin’s lymphoma scheduled for autologous stem cell transplantation underwent PET scans at 1, 72 and 144 h after injection of ~70 MBq 89Zr-ibritumomab tiuxetan and again 2 weeks later after co-injection of 15 MBq/kg or 30 MBq/kg 90Y-ibritumomab tiuxetan. Volumes of interest were drawn over liver, kidneys, lungs, spleen and tumours. Ibritumomab tiuxetan organ absorbed doses were calculated using OLINDA. Red marrow dosimetry was based on blood samples. Absorbed doses to tumours were calculated using exponential fits to the measured data.ResultsThe highest 90Y absorbed dose was observed in liver (3.2 ± 1.8 mGy/MBq) and spleen (2.9 ± 0.7 mGy/MBq) followed by kidneys and lungs. The red marrow dose was 0.52 ± 0.04 mGy/MBq, and the effective dose was 0.87 ± 0.14 mSv/MBq. Tumour absorbed doses ranged from 8.6 to 28.6 mGy/MBq. Correlation between predicted pre-therapy and therapy organ absorbed doses as based on 89Zr-ibritumomab tiuxetan images was high (Pearson correlation coefficient r = 0.97). No significant difference between pre-therapy and therapy tumour absorbed doses was found, but correlation was lower (r = 0.75).ConclusionBiodistribution of 89Zr-ibritumomab tiuxetan is not influenced by simultaneous therapy with 90Y-ibritumomab tiuxetan, and 89Zr-ibritumomab tiuxetan scout scans can thus be used to predict biodistribution and dose-limiting organ during therapy. Absorbed doses to spleen were lower than those previously estimated using 111In-ibritumomab tiuxetan. The dose-limiting organ in patients undergoing stem cell transplantation is the liver.

Considering the different treatment strategy for transformed follicular lymphoma (TF) as opposed to follicular lymphoma (FL), diagnosing transformation early in the disease course is important. There is evidence that 18 F-FDG has utility as a biomarker of transformation. However, quantitative thresholds may require inclusion of homogeneous non-Hodgkin lymphoma subtypes to account for differences in tracer uptake per subtype. Moreover, because proliferation is a hallmark of transformation, 3′-deoxy-3′-18 F-fluorothymidine ( 18 F-FLT) might be superior to 18 F-FDG in this setting. To define the best tracer for detection of TF, we performed a prospective a headto-head comparison of 18 F-FDG and 18 F-FLT in patients with FL and TF. Methods: 18 F-FDG and 18 F-FLT PET scans were obtained in 17 patients with FL and 9 patients with TF. We measured the highest maximum standardized uptake value (SUV max ), defined as the lymph node with the highest uptake per patient, and SUV range , defined as the difference between the SUV max of the lymph node with the highest and lowest uptake per patient. To reduce partial-volume effects, only lymph nodes larger than 3 cm 3 (A50 isocontour) were analyzed. Scans were acquired 1 h after injection of 185 MBq of 18 F-FDG or 18 F-FLT. To determine the discriminative ability of SUV max and SUV range of both tracers for TF, receiver-operatingcharacteristic curve analysis was performed. Results: The highest SUV max was significantly higher for TF than FL for both 18 F-FDG and 18 F-FLT (P , 0.001). SUV range was significantly higher for TF than FL for 18 F-FDG (P 5 0.029) but not for 18 F-FLT (P 5 0.075). The ability of 18 F-FDG to discriminate between FL and TF was superior to that of 18 F-FLT for both the highest SUV max (P 5 0.039) and the SUV range (P 5 0.012). The cutoff value for the highest SUV max of 18 F-FDG aiming at 100% sensitivity with a maximum specificity was found to be 14.5 (corresponding specificity, 82%). For 18 F-FLT, these values were 5.1 and 18%, respectively. When the same method was applied to SUV range , the cutoff values were 5.8 for 18 F-FDG (specificity, 71%) and 1.5 for 18 F-FLT (specificity, 36%). Conclusion: Our data suggest that 18 F-FDG PET is a better biomarker for TF than 18 F-FLT PET. The proposed thresholds of highest SUV max and SUV range should be prospectively validated.

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