18F-FDG or 3'-deoxy-3'-18F-fluorothymidine to detect transformation of follicular lymphoma.

UNLABELLED: 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 head-to-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 (SUVmax), defined as the lymph node with the highest uptake per patient, and SUVrange, defined as the difference between the SUVmax 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 SUVmax and SUVrange of both tracers for TF, receiver-operating-characteristic curve analysis was performed. RESULTS: The highest SUVmax was significantly higher for TF than FL for both (18)F-FDG and (18)F-FLT (P < 0.001). SUVrange was significantly higher for TF than FL for (18)F-FDG (P = 0.029) but not for (18)F-FLT (P = 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 SUVmax (P = 0.039) and the SUVrange (P = 0.012). The cutoff value for the highest SUVmax 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 SUVrange, 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 SUVmax and SUVrange should be prospectively validated.

Biodistribution, radiation dosimetry and scouting of 90Y-ibritumomab tiuxetan therapy in patients with relapsed B-cell non-Hodgkin's lymphoma using 89Zr-ibritumomab tiuxetan and PET.

PURPOSE: Positron emission tomography (PET) with (89)Zr-ibritumomab tiuxetan can be used to monitor biodistribution of (90)Y-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of (90)Y-ibritumomab tiuxetan in humans on the basis of (89)Zr-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of (90)Y-ibritumomab tiuxetan influences biodistribution of (89)Zr-ibritumomab tiuxetan and whether pre-therapy scout scans with (89)Zr-ibritumomab tiuxetan can be used to predict biodistribution of (90)Y-ibritumomab tiuxetan and the dose-limiting organ during therapy. METHODS: Seven 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 (89)Zr-ibritumomab tiuxetan and again 2 weeks later after co-injection of 15 MBq/kg or 30 MBq/kg (90)Y-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. RESULTS: The highest (90)Y 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 (89)Zr-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). CONCLUSION: Biodistribution of (89)Zr-ibritumomab tiuxetan is not influenced by simultaneous therapy with (90)Y-ibritumomab tiuxetan, and (89)Zr-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 (111)In-ibritumomab tiuxetan. The dose-limiting organ in patients undergoing stem cell transplantation is the liver.

Two decades at the cross-roads of biology, physics and epidemiology: lessons learned in [18F-]FDG positron emission tomography in oncology.

[18F-]FDG PET(-CT) is a primarily quantitative imaging technology that is rapidly gaining ground in clinical oncology; initially for staging and diagnosis, and now increasingly as a biomarker of response to therapy. In spite of 20 years of clinical research, there is discussion about its implementation among clinicians, decision-makers and other parties about its implementation. To some extent, this relates to heterogeneity of the PET results and of trial designs, but also to differences in levels of evidence required by various parties. With PET, biological and quantitative imaging is entering the clinical domain. The current subjective perspective reviews these aspects to help clinicians understand biological and physical elements underlying [18F-]FDG PET to increase the clinical awareness of its potential and limitations.