FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0.

The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out,interpret, and document quantitative FDG PET/CT examinations,but will concentrate on the optimisation of diagnostic quality and quantitative information.

Prognostic relevance of response evaluation using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with locally advanced non-small-cell lung cancer.

PURPOSE: The objective of this study was to determine the accuracy of (early) response measurements using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG PET) with respect to survival of patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC) undergoing induction chemotherapy (IC), with a comparative analysis of PET methods. PATIENTS AND METHODS: In a prospective multicenter study, PET was performed in patients before IC and after one and three cycles. Computed tomography (CT) was performed before and after IC. Glucose consumption (metabolic rate of glucose [MRglu]) was measured using Patlak graphical analysis and correlated with simplified methods. Mediastinal lymph node (MLN) status was assessed visually. Cox proportional hazards analysis was used to determine the prognostic relevance of CT and PET measures of response with respect to survival. RESULTS: Complete PET data sets were available in 47 patients. Median survival was 21 months. MLN status after IC by PET predicted survival (hazard ratio [HR], 2.33; 95% CI, 1.04 to 5.22; P = .04) in contrast with CT (HR, 1.87; 95% CI, 0.81 to 4.30; P = .14). Residual MRglu after IC proved to be the best prognostic factor (HR, 1.95; 95% CI, 1.28 to 2.97; P = .002). Multivariate stepwise analysis showed that PET identified prognostically different strata in patients considered responsive according to CT. Residual MRglu after one cycle selected patients with different outcomes (HR, 2.04; 95% CI, 1.18 to 3.52; P = .01). Simplified quantitative 18FDG PET methods were correlated with Patlak graphical analysis during and after therapy (r > or = 0.90). CONCLUSION: 18FDG PET has additional value over CT in monitoring response to IC in patients with stage IIIA-N2 NSCLC, and it seems feasible to predict survival early during IC. Simple semiquantitative and complex PET methods perform equally well.

Measurement of perfusion in stage IIIA-N2 non-small cell lung cancer using H(2)(15)O and positron emission tomography.

PURPOSE: As the interest in antiangiogenesis therapy in oncology is rising, the need for in vivo techniques to monitor such therapy is obvious. Measurement of tumor perfusion using positron emission tomography and H(2)(15)O potentially is such a technique. The objective of the present study was to assess whether it is feasible to measure perfusion in vivo in non-small cell lung cancer (NSCLC) using H(2)(15)O and positron emission tomography. EXPERIMENTAL DESIGN: Fifteen dynamic H(2)(15)O and [(18)F]2-fluoro-2-deoxy-D-glucose ((18)FDG) studies were performed in 10 patients with stage IIIA-N2 NSCLC. Blood flow (BF) data were correlated with simplified methods of analysis (tumor:normal tissue ratio and standardized uptake value) and with glucose metabolism (MR(glu)). RESULTS: (18)FDG data were required for accurate definition of tumor and mediastinal lymph node metastases. There was large intertumor variation in BF. Correlation of simplified methods of analysis with quantitative BF was poor. In addition, BF and MR(glu) were not correlated. CONCLUSION: Measurement of BF in NSCLC using H(2)(15)O and (18)FDG is feasible. Simple uptake analysis, however, cannot be used as an indicator of perfusion. Whether BF can be used for response monitoring needs to be evaluated in a large patient study, where results can be compared with outcome.

Methods to monitor response to chemotherapy in non-small cell lung cancer with 18F-FDG PET.

UNLABELLED: PET using 18F-FDG is a promising technique to monitor response in oncology. Unfortunately, a multitude of analytic methods is in use. To date, it is not clear whether simplified methods could replace complex quantitative methods in routine clinical practice. The aim of this study was to select those methods that would qualify for further assessment in a future prospective response-monitoring study by comparing results with patient outcome. METHODS: Dynamic 18F-FDG PET scans were obtained on 2 groups of patients. First, 10 patients with advanced non-small cell lung cancer (NSCLC) were scanned on consecutive days before treatment to assess test-retest variability. Second, 30 scans were obtained on 19 patients with locally advanced NSCLC as part of an ongoing response-monitoring study. These scans were analyzed by 2 observers to assess observer variability. In addition, these studies were used to compare various methods with the gold standard, full kinetic analysis (nonlinear regression [NLR]). RESULTS: Using an image-derived input function, NLR showed excellent test-retest and observer agreement confirming that it could be used as a gold standard method. From a total of 34 analytic methods, 10 showed good correlation with NLR. Taking into account the degree of complexity of the methods, 4 remain for further evaluation. CONCLUSION: The optimal method for analysis of 18F-FDG PET data was determined for several levels of complexity. Four methods need to be evaluated further to determine the optimal trade-off between simplicity and accuracy for routine clinical practice.

Positron emission tomography in the management of non-small cell lung cancer.

In the past 10 years, FDG-PET has become an important imaging modality in NSCLC. Its indication in the assessment of lung nodules and staging is based on large prospective experience, further supported by some meta-analyses. This evidence has important consequences for patient management, which recently was proved in a randomized trial that showed a reduction in the number of futile thoracotomies by preoperative PET. The use of FDG-PET could become more widespread when commercial isotope distributors are able to deliver FDG so that an on-site cyclotron is no longer a prerequisite. FDG has a half-life of 110 minutes, so a practical distribution radius of 200 km should be feasible. Current indications for PET in the staging of newly diagnosed NSCLC are mainly the patients who are considered to be candidates for radical treatment. The technique does not have a clinical indication in other patients--for example, when metastatic lymph nodes are detected at clinical examination, when a simple ultrasound study already points to diffuse hepatic metastases, or in cases of poor performance status. PET also has prognostic value; it can be used for the evaluation of response or restaging after radiotherapy or chemotherapy and for early detection of relapse. The combination of CT and PET improves radiotherapy planning and it is to be expected that combined CT-PET-guided planning devices will further refine three-dimensional conformal radiotherapy. Finally, a whole new field of application of PET in molecular biology using new radiopharmaceutics is in development. FDG, with its possibility to study tumor glucose metabolism, has paved the way for PET in clinical oncology. It is hoped that PET examinations with new molecular tracers will allow ever better specificity and become sufficiently reliable and manageable to evaluate receptors, transport proteins, and intracellular enzymes so that very early response monitoring during chemotherapy or radiotherapy, evaluation of novel molecular-targeted lung cancer therapies, or even gene therapy becomes possible. New tracers that have showed their promise in early clinical studies include 18F-fluorothymidine (a proliferation marker that might give better specificity in the assessment of solitary pulmonary nodules or better accuracy in the evaluation of early response), (99m)Tc-Annexin V (Apomate; an apoptosis-imaging agent that could be correlated with overall and progression-free survival in phase I data), or 18F-fluoromisonidazole (which can be used to quantify regional hypoxia in human tumors with PET).

Additional value of whole-body fluorodeoxyglucose positron emission tomography in the detection of distant metastases of non-small-cell lung cancer.

The purpose of this work was to evaluate the additional value of whole-body positron emission tomography (WB-PET) in the distant staging of non-small-cell lung cancer (NSCLC). One hundred forty-four patients with NSCLC in whom conventional staging (CS) was negative or equivocal for metastases, and who underwent WB-PET as part of their initial work-up, were retrospectively analyzed. Conventional staging consisted of thoracic computed tomography (CT), upper abdominal ultrasound and/or CT, and bone scintigraphy or brain CT on indication. Final M stage was based on histology, additional imaging, or follow-up of = 18 months. An additional lesion suspect for metastasis was found on WB-PET in 11 patients. This was true positive in 7 (3 bone, 1 retroperitoneal lymph nodes, 1 lung, and 2 asymptomatic coexisting colorectal cancer) and false positive in 4 patients (3 bowel, 1 breast). Twenty-four lesions in 21 patients remained equivocal after CS. Whole- body PET correctly characterized 20 lesions in 18 patients as true positive (n = 1) or true negative (n = 19). Whole-body PET was false positive in one patient (adrenal adenoma) and false negative in 2 patients (2 bone, 1 lung lesion). Despite negative results of modern CS and WB-PET, 16 of 86 patients (19%) who underwent a curative resection, experienced a systemic relapse. After thorough modern CS, WB-PET correctly detected additional distant malignant lesions in only 5% of the patients, while the combined staging strategy probably still misses micrometastatic disease in one fifth of the patients. The most important contribution of WB-PET was its ability to exclude malignancy in the majority of distant lesions with equivocal CS.

Added value of baseline 18F-FDG uptake in serial 18F-FDG PET for evaluation of response of solid extracerebral tumors to systemic cytotoxic neoadjuvant treatment: a meta-analysis.

UNLABELLED: The purpose of this study was to test the hypothesis that the level of baseline (18)F-FDG uptake in the primary tumor adds value to its relative change in (18)F-FDG uptake in serial PET scans in predicting the histopathologic response to systemic cytotoxic neoadjuvant treatment of patients with solid extracerebral tumors. METHODS: We performed a literature search from January 1995 through November 2008 using PubMed and Embase. Two reviewers independently selected eligible studies for possible inclusion in the meta-analysis by reviewing titles and abstracts. Inclusion criteria were at least 10 patients, (18)F-FDG PET before and after therapy, (18)F-FDG PET performed with the intention of monitoring the response of solid extracerebral tumors in humans to cytotoxic neoadjuvant systemic therapy, attenuation-corrected (18)F-FDG PET studies, and studies presenting individual patient data (PET results and histopathologic reference test after treatment). Multilevel logistic regression was used to assess the effect of relative change of (18)F-FDG uptake ([baseline - end]/baseline) and baseline (18)F-FDG uptake value with type of tumor and type of treatment as level 1 covariates. RESULTS: Nineteen studies (all observational; a total of 438 patients [median, 23 patients per study; range, 10-40]) were included, aiming at the accuracy of PET versus histopathology. To quantify PET, maximum standardized uptake value (SUV) was used in 6 studies, mean SUV in 7, SUV (subtype unclear) in 1, tumor-to-background ratio in 3, and dose uptake ratio in 1. The average overall histopathologic response rate was 0.47 (median, 0.50), ranging from 0.17 to 0.88. The relative change in (18)F-FDG uptake was the strongest indicator (P < 0.0001) for tumor response. Baseline (18)F-FDG was not significantly associated as a main factor; however, a significant interaction of baseline uptake and relative change after therapy was observed (P < 0.001). CONCLUSION: Relative change in (18)F-FDG uptake was the strongest indicator for tumor response, but the level of baseline (18)F-FDG uptake in the primary tumor provided additional information about prediction of response to therapy. These data corroborate and extend the need for standardization, quality assurance, and control of PET studies quantifying (18)F-FDG in oncologic treatment monitoring.

FDG positron emission tomography/computed tomography scan may identify mantle cell lymphoma patients with unusually favorable outcome.

OBJECTIVE: Patients diagnosed with mantle cell lymphoma (MCL) have generally poor prognosis, but a minority have a longer survival. There are no markers to identify this group and no generally established prognostic index for MCL. Our objective was to assess the prognostic value of the staging FDG PET/computed tomography (CT) scan. METHODS: We retrospectively analyzed initial scans performed at three institutions on biopsy-proven, cyclin D (+) MCL patients. The association of the SUVmax of the 'hottest focus' with overall survival (OS) and failure-free survival (FFS) was evaluated. Receiver operating characteristic analysis of SUVmax versus survival was used to establish a cut-off point of 4.83. In addition, PET findings were compared with contrast-enhanced CT performed within 3 weeks in patients from one institution. RESULTS: Both the OS and FFS for patients with SUVmax greater than 5 were significantly decreased (P<0.01 and <0.001, respectively) as compared with the patients with SUV < or = 5. The 5-year OS for group with SUVmax < or = 5 was 87.7% and for SUVmax greater than 5 it was 34%. For SUVmax < or = 5, the median FFS was 45.3 months as compared with 10.6 months for SUVmax greater than 5. PET changed the stage as compared with CT alone in 45% of patients. CONCLUSION: Staging FDG PET/CT is superior to CT and may be used in the future for identification of a subset of MCL patients with a better outcome than otherwise expected.