Quantitative 18F-DOPA PET/CT in pheochromocytoma: the relationship between tumor secretion and its biochemical phenotype.

INTRODUCTION: 18F-FDOPA illustrates the properties of uptake and storage of catecholamines in pheochromocytomas (PHEOs). Until now, the relationship between 18F-FDOPA quantitative parameters and a PHEO secretory profile has not been specifically evaluated. MATERIALS AND METHODS: Fifty-six patients (56% females, median age: 47.5 yrs) with non-metastatic PHEO, evaluated by 18F-FDOPA PET/CT, were included in this retrospective study. Forty-five patients had negative genetic testing (80.4%); five patients (8.9%) had RET, two patients (3.6%) had SDHB, two had SDHD (3.6%), one patient (1.8%) had NF1, and one patient had a VHL (1.8%) mutation. Correlation between 18F-FDOPA metabolic parameters (tumor SUVmax, tumor SUVmean, tumor SUVmax/liver SUVmax, MTV 42%, total lesion uptake), urinary metanephrines (MNs), and plasma chromogranin A (CgA) were evaluated. RESULTS: All patients had positive 18F-FDOPA PET/CT. On univariate analysis, there was a strong correlation between all metabolic parameters and urinary MNs and plasma chromogranin A (CgA). The highest correlations were observed between total lesion (TL) uptake and the value of urinary MNs regardless of their nature (p = 8.10-15 and r = 0.80) and between MTV 42% and plasma CgA levels (p = 2.10-9, r = 0.74). On multivariate analysis, the correlation of uptake parameters and CgA levels did not persist further due to the relation of CgA and tumor diameter. A correlation between TL uptake and the normetanephrine/metanephrine ratio (NMN/MN) was also found, a finding that was in accordance with in vitro studies, which were found to have a higher catecholamine content in epinephrine producing PHEOs. CONCLUSION: This retrospective study shows a correlation between 18F-FDOPA uptake, especially using TL uptake, urinary MNs, and a PHEO biochemical phenotype. This illustrates that beyond its localization value, 18F-FDOPA PET further enables PHEO characterization at a specific metabolic level.

Local Recurrence Risk Score to Predict Relapse after Stereotactic Body Radiation Therapy for Lung Tumors.

Background: After stereotactic body radiation therapy (SBRT) for lung tumors, follow-up CT scans remain a pitfall. The early detection of local relapse is essential to propose a new treatment. We aim to create a local recurrence predictive score using pre- and post-therapeutic imaging criteria and test it on a validation cohort. Methods: Between February 2011 and July 2016, lung tumors treated by SBRT with available pretreatment fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) and follow-up CT scans were retrospectively analyzed. The risk factors associated with relapse were identified by univariate logistic regression on a train cohort. The score was created using these factors, merging clinical and imaging criteria associated with local relapse, and then tested on an independent validation cohort. Overall and local relapse-free survival at 1 and 3 years were recorded. Results: Twenty-eight patients were included in the train cohort and ten in the derivation cohort (male 74%, median age 70 ± 12 years). Five variables significantly associated with local recurrence (female gender; sequential enlargement; craniocaudal growing; bulging margins; standardized uptake value (SUVmax > 5.5)) were combined to create the score on five points. With the threshold >2.5/5, the sensitivity and specificity of the score on the validation cohort were 100% and 88%, respectively. Overall survival and local relapse-free survival at 1 and 3 years were 89% and 42%, and 89% and 63%, respectively. Conclusion: The local recurrence risk score created has high sensitivity (100%) and specificity (88%), upon independent validation cohort, to detect local relapse. This score is easy to use in daily clinical practice.

18F-fluorodeoxyglucose positron emission tomography/computed tomography for the diagnosis of native valve infective endocarditis: A prospective study.

BACKGROUND: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) has recently been added as a major criterion in the European Society of Cardiology (ESC) 2015 infective endocarditis guidelines. PET/CT is currently used in patients with suspected prosthetic valve and cardiac device-related endocarditis. However, the value of the ESC classification and the clinical impact of PET findings are unknown in patients with native valve endocarditis (NVE). AIMS: Our aims were: to assess the value of the ESC criteria (including PET/CT) in NVE; to determine the usefulness of PET/CT concerning embolic detection; and to describe a new PET/CT feature (diffuse splenic uptake). METHODS: Between 2012 and 2017, 75 patients with suspected NVE were included prospectively, after exclusion of patients with uninterpretable or unfeasible PET/CT. Using gold standard expert consensus, 63 cases of infective endocarditis were confirmed and 12 were rejected. RESULTS: Significant valvular uptake was observed in 11 of 63 patients with definite NVE and in no patients who had the diagnosis of infective endocarditis rejected (sensitivity 17.5%, specificity 100%). Among the 63 patients with NVE, a peripheral embolism or mycotic aneurysm was observed in 20 (31.7%) cases. Application of the ESC criteria increased Duke criteria sensitivity from 63.5% to 69.8% (P<0.001), without a change in specificity. Diffuse splenic uptake was observed in 39 (52.0%) patients, including 37 (58.7%) with a final diagnosis of NVE (specificity 83.3%). CONCLUSIONS: 18F-FDG PET/CT has poor sensitivity but high specificity in the diagnosis of NVE. The usefulness of 18F-FDG PET/CT is high for embolic detection. Diffuse splenic uptake represents a possible new diagnostic criterion for NVE.

A new methodology to derive 3D kinetic parametric FDG PET images based on a mathematical approach integrating an error model of measurement.

BACKGROUND: In FDG-PET, SUV images are hampered by large potential biases. Our aim was to develop an alternative method (ParaPET) to generate 3D kinetic parametric FDG-PET images easy to perform in clinical oncology. METHODS: The key points of our method are the use of a new error model of PET measurement extracted from a late dynamic PET acquisition of 15 min, centered over the lesion and an image-derived input function (IDIF). The 15-min acquisition is reconstructed to obtain five images of FDG mean activity concentration and images of its variance to model errors of PET measurement. Our approach is carried out on each voxel to derive 3D kinetic parameter images. ParaPET was evaluated and compared to Patlak analysis as a reference. Hunter and Barbolosi methods (Barbolosi-Bl: with blood samples or Barbolosi-Im: with IDIF) were also investigated and compared to Patlak. Our evaluation was carried on Ki index, the net influx rate and its maximum value in the lesion (Ki,max). RESULTS: This parameter was obtained from 41 non-small cell lung cancer lesions associated with 4 to 5 blood samples per patient, required for the Patlak analysis. Compare to Patlak, the median relative difference and associated range (median; [min;max]) in Ki,max estimates were not statistically significant (Wilcoxon test) for ParaPET (- 3.0%; [- 31.9%; 47.3%]; p = 0.08) but statistically significant for Barbolosi-Bl (- 8.0%; [- 30.8%; 53.7%]; p = 0.001), Barbolosi-Im (- 7.9%; [- 38.4%; 30.6%]; p = 0.007) or Hunter (32.8%; [- 14.6%; 132.2%]; p < 10- 5). In the Bland-Altman plots, the ratios between the four methods and Patlak are not dependent of the Ki magnitude, except for Hunter. The 95% limits of agreement are comparable for ParaPET (34.7%), Barbolosi-Bl (30.1%) and Barbolosi-Im (30.8%), lower to Hunter (81.1%). In the 25 lesions imaged before and during the radio-chemotherapy, the decrease in the FDG uptake (ΔSUVmax or ΔKi,max) is statistically more important (p < 0.02, Wilcoxon one-tailed test) when estimated from the Ki images than from the SUV images (additional median variation of - 2.3% [- 52.6%; + 19.1%] for ΔKi,max compared to ΔSUVmax). CONCLUSION: None of the four methodologies is yet ready to replace the Patlak approach, and further improvements are still required. Nevertheless, ParaPET remains a promising approach, offering a non-invasive alternative to methods based on multiple blood samples and only requiring a late PET acquisition. It allows deriving Ki values, highly correlated and presenting the lowest relative bias with Patlak estimates, in comparison to the other methods we evaluated. Moreover, ParaPET gives access to quantitative information at the pixel level, which needs to be evaluated in the perspective of radiomic and tumour response. TRIAL REGISTRATION: NCT 02821936 ; May 2016.