Découverte fortuite de fixations colorectales focales du FDG en TEP/TDM : corrélation aux données de la coloscopie

PurposeFDG-PET is an established tool for the diagnosis of recurrent or metastatic colorectal carcinoma. Several case series suggest that FDG-PET often detects incidental adenomatous polyps or colorectal adenocarcinomas. The aim of this study was to correlate unexpected colorectal foci of FDG uptake to pathology findings after systematic colonoscopy.Patients and methodsWe reviewed the records of 3541 patients who underwent FDG PET/CT in our institution over a 30-month period for the assessment of a known or suspected malignancy. In 85 of them, incidental, nodular shaped and well-circumscribed foci of abnormal uptake were identified in the area of the colon or rectum. Patients with segmental or diffuse abnormal colorectal uptake were excluded, as well as patients with known benign or malignant colorectal disease. Colonoscopy and complete pathology report was available in 29 patients. Maximal standardized uptake value (SUV_max) was measured in all lesions.ResultsUnexpected colorectal foci of FDG uptake were associated with colonoscopic abnormalities in 23 patients (true positive rate: 79 %). Adenocarcinomas were found in six patients (SUV_max = 7.3 ± 2.6), tubulous adenomas in four patients (SUV_max = 7.3 ± 4.9) and tubulovillous adenomas in 12 patients (SUV_max = 4.2 ± 1.1). Hyperplasic polyps with no sign of dysplasia were found in the last patient (SUV_max = 3.3). Concomitant CT abnormalities were found on PET/CT fusion in eight patients and consisted of wall thickening (n = 5) or nodular mass (n = 3). Conversely, PET was falsely positive in six patients (21 %), with no concomitant CT abnormalities and no abnormal findings at endoscopy (SUV_max = 6.2 ± 2.8, no significant difference with true positive lesions).ConclusionOur findings emphasize the need to perform a colonoscopy in front of incidental nodular colorectal foci of FDG uptake because malignant or pre-malignant neoplasms, which are not clinically apparent, are found in more than three-quarter of cases.     

Interpretation of the krypton-81m dynamic series: the distribution of a tidal breath

Lung scans during cyclic breathing of krypton-81m, an isotope with a 13-s half-life, were acquired in "list mode," where both temporal and spatial information are preserved. Subjects in the left lateral decubitus position breathed with two tidal volumes at each of two frequencies. Profiles of total activity over the acquisition period were examined. They showed little effect of frequency or tidal volume on the distribution of air between dependent and non-dependent regions. Dynamic series for ensemble-averaged breaths were constructed. The regional flow per unit volume was shown to correspond to the time derivative of the regional activity of the dynamic series divided by the corresponding activity. Both the relative timing of the gas flow to different lung regions and the flow per unit volume as a function of time were obtained from the dynamic series. The dependent lung was seen to be better ventilated throughout the respiratory cycle except for brief periods at the start of inspiration and the end of expiration. Most of the dead-space gas can be construed to enter and leave the dependent lung.     

New selective carbonic anhydrase IX inhibitors: Synthesis and pharmacological evaluation of diarylpyrazole-benzenesulfonamides

Carbonic anhydrase (CA) IX expression is increased upon hypoxia and has been proposed as a therapeutic target since it has been associated with poor prognosis, tumor progression and pH regulation. We report the synthesis and the pharmacological evaluation of a new class of human carbonic anhydrase (hCA) inhibitors, 4-(5-aryl-2-hydroxymethyl-pyrazol-1-yl)-benzenesulfonamides. A molecular modeling study was conducted in order to simulate the binding mode of this new family of enzyme inhibitors within the active site of hCA IX. Pharmacological studies revealed high hCA IX inhibitory potency in the parameters nanomolar range. This study showed that the position of sulfonamide group in meta of the 1-phenylpyrazole increase a selectivity hCA IX versus hCA II of our compounds. An in vitro antiproliferative screening has been performed on the breast cancer MDA-MB-231 cell using doxorubicin as cytotoxic agent and in presence of selected CA IX inhibitor. The results shown that the cytotoxic efficiency of doxorubicin in an hypoxic environment, expressed in IC₅₀ value, is restored at 20% level with 1 μM CA IX inhibitor.     

Effects of sustained exercise on pulmonary clearance of aerosolized 99mTc-DTPA

The effects of intensive prolonged exercise on the pulmonary clearance rate of aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) and pulmonary mechanics were studied in seven healthy nonsmoking volunteers. 99mTc-DTPA clearance and pulmonary mechanics (lung volumes and compliance) were assessed before and after 75 min of constant-load exercise performed on a treadmill, corresponding to 75% of maximal O2 uptake. Because both clearance measurements were made in similar conditions of pulmonary blood flow, respiratory rate, and tidal volume, changes in clearance rate can be assumed to represent changes of alveolar epithelial permeability. After exercise, total, apical, and basal clearance were significantly increased (P less than 0.01, 0.05, and 0.05, respectively) and the increases in total clearance and tidal volume observed during exercise were significantly correlated (P less than 0.05). In contrast, no significant change was found in pulmonary mechanics. These results show that prolonged intensive exercise induces an increase in epithelial permeability, which appears to be related to the mechanical effects of sustained increased ventilation. Because no change was evidenced in pulmonary volumes or in lung elasticity, our results suggest that this increase may result from alteration of the intercellular tight junctions rather than from a surfactant deficiency.     

[F-18]-Fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose positron emission tomography as a tool for early detection of immunotherapy response in a murine B cell lymphoma model

[F-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) is a non-invasive imaging technique which has recently been validated for the assessment of therapy response in patients with aggressive non-Hodgkin’s lymphoma. Our objective was to determine its value for the evaluation of immunotherapy efficacy in immunocompetent Balb/c mice injected with the A20 syngeneic B lymphoma cell line. The high level of in vitro FDG uptake by A20 cells validated the model for further imaging studies. When injected intravenously, the tumour developed as nodular lesions mostly in liver and spleen, thus mimicking the natural course of an aggressive human lymphoma. FDG-PET provided three-dimensionnal images of tumour extension including non-palpable lesions, in good correlation with ex vivo macroscopic examination. When mice were pre-immunized with an A20 cell lysate in adjuvant before tumour challenge, their significantly longer survival, compared to control mice, were associated with a lower incidence of lymphoma visualized by PET at different time points. Estimation of tumour growth and metabolism using the calculated tumour volumes and maximum standardized uptake values, respectively, also demonstrated delayed lymphoma development and lower activity in the vaccinated mice. Thus, FDG-PET is a sensitive tool relevant for early detection and follow-up of internal tumours, allowing discrimination between treated and non-treated small animal cohorts without invasive intervention. C. Chaise and E. Itti contributed equally to the work.     

Overexpression of p75NTR increases survival of breast cancer cells through p21waf1

The p75 neurotrophin receptor (p75^NTR) plays a critical role in various neuronal and non-neuronal cell types by regulating cell survival, differentiation and proliferation. To evaluate the influence of p75^NTR in breast cancer development, we have established and characterized breast cancer cells which stably overexpress p75^NTR. We showed that p75^NTR overexpression per se promoted cell survival to apoptogens with a concomitant slowdown of cell growth. The pro-survival effect is associated with an increased expression of the inhibitor of apoptosis protein-1 (c-IAP1), a decrease of TRAIL-induced cleavage of PARP, procaspase 9 and procaspase 3, and a decrease of cytochrome C release from the mitochondria. The anti-proliferative effect is due to a cell accumulation in G0/G1, associated with a decrease of Rb phosphorylation and an increase of p21^waf1. Interestingly, inhibition of p21^waf1 with siRNA not only restores proliferation but also abolishes the pro-survival effect of p75^NTR, indicating the key role of p21^waf1 in the biological functions of p75^NTR. Finally, using a SCID mice xenograft model, we showed that p75^NTR overexpression favors tumor growth and strongly increases tumor resistance to anti-tumoral treatment.Together, our findings suggest that p75^NTR overexpression in breast tumor cells could favor tumor survival and contribute to tumor resistance to drugs. This provides a rationale to consider p75^NTR as a potential target for the future design of innovative therapeutic strategies.     

Lung epithelial permeability to aerosolized solutes: relation to position

The lung epithelial permeability to inhaled solutes is primarily attributed to the degree of distension of the interepithelial junctions and thus of the alveolar volume. To assess this hypothesis, a submicronic aerosol of technetium-99m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) was inhaled by eight normal subjects in left lateral decubitus (LLD). The regional lung clearance of 99mTc-DTPA was measured in LLD, then in right lateral decubitus (RLD) to reverse the relative distension of the alveoli. Although in LLD the deposition of the aerosol is the greatest in the gravity-dependent regions of the left lung, their 99mTc-DTPA clearances are significantly lower than those of the nondependent regions of the right lung (0.7 +/- 0.3 vs. 2 +/- 0.8%/min, P less than 0.001). In RLD, these regions placed in opposite positions significantly reversed their clearances (1.6 +/- 0.8 vs. 0.6 +/- 0.2%/min, P less than 0.001). Results indicate in lateral decubitus a gravity gradient of 99mTc-DTPA clearances independent of the aerosol deposition. This gradient of epithelial permeability to solutes appears to be influenced by the gradient of alveolar volume.