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Interim 18F-fluorodeoxyglucose positron emission tomography (Interim- 18F-FDG-PET,hereafter I-PET) has the potential to guide treatment of patients with diffuse large B-celllymphoma (DLBCL) if the prognostic value is known. The aim of this study was to determinethe optimal timing and response criteria for evaluating prognosis with I-PET in DLBCL.Individual patient data from 1692 patients with de novo DLBCL were combined and scans were harmonized. I-PET was performed at various time points during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Scans were interpreted using the Deauville score (DS) and change in maximum standardized uptake value (DSUVmax ). Multilevel Cox proportional hazards models corrected for International Prognostic Index (IPI) score were used to study the effects oftiming and response criteria on 2-year progression-free survival (PFS). I-PET after 2 cycles (I-PET2) and I-PET4 significantly discriminated good responders from poor responders, with the highest hazard ratios (HRs) for I-PET4. Multivariable HRs for a PET-positive result at I-PET2 and I-PET4 were 1.71 and 2.95 using DS4-5, 4.91 and 6.20 using DS5, and 2.93 and 4.65 using DSUVmax , respectively. DSUVmax identified a larger proportion of poor respondersthan DS5 did. For all criteria, the negative predictive value was >80%, and positivepredictive values ranged from 30% to 70% at I-PET2 and I-PET4. Unlike I-PET1, I-PET3discriminated good responders from poor responders using DS4-5 and DS5 thresholds (HRs,2.94 and 4.67, respectively). I-PET2 and I-PET4 predict good response equally during R-CHOPtherapy in DLBCL. Optimal timing and response criteria depend on the clinical context. Goodresponse at I-PET2 is suggested for de-escalation trials, and poor response using DSUVmax atI-PET4 is suggested for randomized trials that are evaluating new therapies

PURPOSE: In-vivo quantification of tumor uptake of 89-zirconium (89Zr)-labelled monoclonal antibodies (mAbs) with PET provides a potential tool in strategies to optimize tumor targeting and therapeutic efficacy. A specific challenge for 89Zr-immuno-PET is low tumor contrast. This is expected to result in interobserver variation in tumor delineation. Therefore, the aim of this study was to determine interobserver reproducibility of tumor uptake measures by tumor delineation on 89Zr-immuno-PET scans.METHODS: Data were obtained from previously published clinical studies performed with 89Zr-rituximab, 89Zr-cetuximab and 89Zr-trastuzumab. Tumor lesions on 89Zr-immuno-PET were identified as focal uptake exceeding local background by a nuclear medicine physician. Three observers independently manually delineated volumes of interest (VOI). Maximum, peak and mean standardized uptake values (SUVmax, SUVpeak and SUVmean) were used to quantify tumor uptake. Interobserver variability was expressed as the coefficient of variation (CoV). The performance of semi-automatic VOI delineation using 50% of background-corrected ACpeak was described.RESULTS: In total, 103 VOI were delineated (3-6 days post injection (D3-D6)). Tumor uptake (median, interquartile range) was 9.2 (5.2-12.6), 6.9 (4.0-9.6) and 5.5 (3.3-7.8) for SUVmax, SUVpeak and SUVmean. Interobserver variability was 0% (0-12), 0% (0-2) and 7% (5-14), respectively (n = 103). The success rate of the semi-automatic method was 45%. Inclusion of background was the main reason for failure of semi-automatic VOI.CONCLUSIONS: This study shows that interobserver reproducibility of tumor uptake quantification on 89Zr-immuno-PET was excellent for SUVmax and SUVpeak using a standardized manual procedure for tumor segmentation. Semi-automatic delineation was not robust due to limited tumor contrast.

Purpose This pilot study aimed to determine interobserver reliability and ease of use of three workflows for measuring metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in diffuse large B cell lymphoma (DLBCL). Procedures Twelve baseline [18F]FDG PET/CT scans from DLBCL patients with wide variation in number and size of involved organs and lymph nodes were selected from the international PETRA consortium database. Three observers analyzed scans using three workflows. Workflow A: user-defined selection of individual lesions followed by four automated segmentations (41%SUVmax, A50%SUVpeak, SUV≥2.5, SUV≥4.0). For each lesion, observers indicated their “preferred segmentation.” Individually selected lesions were summed to yield total MTV and TLG. Workflow B: fully automated preselection of [18F]FDG-avid structures (SUV≥4.0 and volume≥3ml), followed by removing non-tumor regions with single mouse clicks. Workflow C: preselected volumes based on Workflow B modified by manually adding lesions or removing physiological uptake, subsequently checked by experienced nuclear medicine physicians. Workflow C was performed 3 months later to avoid recall bias from the initial Workflow B analysis. Interobserver reliability was expressed as intraclass correlation coefficients (ICC). Results Highest interobserver reliability in Workflow A was found for SUV≥2.5 and SUV≥4.0 methods (ICCs for MTV 0.96 and 0.94, respectively). SUV≥4.0 and A50%Peak were most and SUV≥2.5 was the least preferred segmentation method. Workflow B had an excellent interobserver reliability (ICC = 1.00) for MTV and TLG. Workflow C reduced the ICC for MTV and TLG to 0.92 and 0.97, respectively. Mean workflow analysis time per scan was 29, 7, and 22 min for A, B, and C, respectively. Conclusions Improved interobserver reliability and ease of use occurred using fully automated preselection (using SUV≥4.0 and volume≥3ml, Workflow B) compared with individual lesion selection by observers (Workflow A). Subsequent manual modification was necessary for some patients but reduced interobserver reliability which may need to be balanced against potential improvement on prognostic accuracy.

Treatment for rheumatoid arthritis (RA) should be started as early as possible to prevent destruction of bone and cartilage in affected joints. A new diagnostic tool for both early diagnosis and therapy monitoring would be valuable to reduce permanent joint damage. Positron emission tomography (PET) imaging of macrophages is a previously demonstrated non-invasive means to visualize (sub)clinical arthritis in RA patients. We developed a kinetic model to quantify uptake of the macrophage tracer [11C]DPA-713 (N,N-diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo [1,5-a]pyrimidin-3-yl]acetamide) in arthritic joints of RA patients and to assess the performance of several simplified methods. Dynamic [11C]DPA-713 scans of 60 min with both arterial and venous blood sampling were performed in five patients with clinically active disease. [11C]DPA-713 showed enhanced uptake in affected joints of RA patients, with tracer uptake levels corresponding to clinical presence and severity of arthritis. The optimal quantitative model for assessment of [11C]DPA-713 uptake was the irreversible two tissue compartment model (2T3k). Both Ki and standardized uptake value (SUV) correlated with the presence of arthritis in RA patients. Using SUV as an outcome measure allows for a simplified static imaging protocol that can be used in larger cohorts.