Combination of MRI and dynamic FET PET for initial glioma grading.

AIM: MRI and PET with 18F-fluoro-ethyl-tyrosine (FET) have been increasingly used to evaluate patients with gliomas. Our purpose was to assess the additive value of MR spectroscopy (MRS), diffusion imaging and dynamic FET-PET for glioma grading. PATIENTS, METHODS: 38 patients (42 ± 15 aged, F/M: 0.46) with untreated histologically proven brain gliomas were included. All underwent conventional MRI, MRS, diffusion sequences, and FET-PET within 3±4 weeks. Performances of tumour FET time-activity-curve, early-to-middle SUVmax ratio, choline / creatine ratio and ADC histogram distribution pattern for gliomas grading were assessed, as compared to histology. Combination of these parameters and respective odds were also evaluated. RESULTS: Tumour time-activity-curve reached the best accuracy (67%) when taken alone to distinguish between low and high-grade gliomas, followed by ADC histogram analysis (65%). Combination of time-activity-curve and ADC histogram analysis improved the sensitivity from 67% to 86% and the specificity from 63-67% to 100% (p < 0.008). On multivariate logistic regression analysis, negative slope of the tumour FET time-activity-curve however remains the best predictor of high-grade glioma (odds 7.6, SE 6.8, p = 0.022). CONCLUSION: Combination of dynamic FET-PET and diffusion MRI reached good performance for gliomas grading. The use of FET-PET/MR may be highly relevant in the initial assessment of primary brain tumours.

The role of PET/CT in cervical cancer.

In locally advanced cervical cancer, (18)F-fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET/CT) has become important in the initial evaluation of disease extent. It is superior to other imaging modalities for lymph node status and distant metastasis. PET-defined cervical tumor volume predicts progression-free and overall survival. Higher FDG uptake in both primary and regional lymph nodes is strongly predictive of worse outcome. FDG-PET is useful for assessing treatment response 3 months after completing concurrent chemo-radiotherapy (CRT) and predicting long-term survival, and in suspected disease recurrence. In the era of image-guided adaptive radiotherapy, accurately defining disease areas is critical to avoid irradiating normal tissue. Based on additional information provided by FDG-PET, radiation treatment volumes can be modified and higher doses to FDG-positive lymph nodes safely delivered. FDG-PET/CT has been used for image-guided brachytherapy of FDG-avid tumor volume, while respecting low doses to bladder and rectum. Despite survival improvements due to CRT in cervical cancer, disease recurrences continue to be a major problem. Biological rationale exists for combining novel non-cytotoxic agents with CRT, and drugs targeting specific molecular pathways are under clinical development. The integration of these targeted therapies in clinical trials, and the need for accurate predictors of radio-curability is essential. New molecular imaging tracers may help identifying more aggressive tumors. (64)Cu-labeled diacetyl-di(N(4)-methylthiosemicarbazone) is taken up by hypoxic tissues, which may be valuable for prognostication and radiation treatment planning. PET/CT imaging with novel radiopharmaceuticals could further impact cervical cancer treatment as surrogate markers of drug activity at the tumor microenvironment level. The present article reviews the current and emerging role of PET/CT in the management of cervical cancer.

Fréquence des incidentalomes lors d'un examen PET/CT effectué pour une pathologie oncologique

Contexte¦Le PET/CT au 18Fluor (FDG) fait aujourd'hui partie intégrante des moyens diagnostiques¦à disposition pour la stadification des cancers suspectés ou connus. Il n'est pas rare de¦découvrir des lésions fortuites.¦Objectifs¦Notre but était de déterminer la fréquence des lésions tumorales ou non, cliniquement¦silencieuses (incidentalomes), chez des patients consécutifs non sélectionnés examinés¦par PET/CT au FDG pour un cancer connu ou supposé au sein du bassin populationnel¦du CHUV.¦Méthode¦Nous avons rétrospectivement lu les 1226 des rapports d'examens faits d'août 2009 à¦juillet 2010 pour toute indication oncologique et relevé les lésions de découverte¦fortuite et leur localisation, avant de rechercher leur investigation et leur prise en¦charge.¦Résultats¦Nous avons retenu 309 lésions fortuites chez 260 patients (25,2% des rapports lus),¦dont 141 chez 127 patients investiguées. Ont été relevés 31 patients présentant 32¦incidentalomes (2,6%), dont 6 étaient malins, 6 pré-malins et 20 bénins, soit un taux de¦1% pour les malins et pré-malins. Les sites les plus fréquents étaient les mêmes que¦dans la littérature, à savoir la thyroïde, le poumon, la sphère colorectale (lésions prémalignes¦uniquement) et les lymphomes. Pour ces trois derniers, les lésions étaient¦moins fréquentes que ce qui est rapporté. Tous ces foyers sont à investiguer¦soigneusement, afin de différencier une nouvelle atteinte d'une métastase.¦Conclusion¦En tant que première étude suisse sur le sujet, nous obtenons 1% d'incidentalomes¦(pré)malins, soit l'équivalent de la limite inférieure de la littérature, dans des sites¦similaires. Une amélioration serait possible en augmentant l'attention portée aux lésions¦jugées peu significatives. A l'instar de nombreuses autres études, nous sommes aussi¦confrontés au problème lié à l'interprétation des foyers de captation et à la nonspécificité¦du FDG.

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PET-measured responses of MBF to cold pressor testing correlate with indices of coronary vasomotion on quantitative coronary angiography.

The aims of this study were to determine whether responses in myocardial blood flow (MBF) to the cold pressor testing (CPT) method noninvasively with PET correlate with an established and validated index of flow-dependent coronary vasomotion on quantitative angiography. METHODS: Fifty-six patients (57 +/- 6 y; 16 with hypertension, 10 with hypercholesterolemia, 8 smokers, and 22 without coronary risk factors) with normal coronary angiograms were studied. Biplanar end-diastolic images of a selected proximal segment of the left anterior descending artery (LAD) (n = 27) or left circumflex artery (LCx) (n = 29) were evaluated with quantitative coronary angiography in order to determine the CPT-induced changes of epicardial luminal area (LA, mm(2)). Within 20 d of coronary angiography, MBF in the LAD, LCx, and right coronary artery territory was measured with (13)N-ammonia and PET at baseline and during CPT. RESULTS: CPT induced on both study days comparable percent changes in the rate x pressure product (%DeltaRPP, 37% +/- 13% and 40% +/- 17%; P = not significant [NS]). For the entire study group, the epicardial LA decreased from 5.07 +/- 1.02 to 4.88 +/- 1.04 mm(2) (DeltaLA, -0.20 +/- 0.89 mm(2)) or by -2.19% +/- 17%, while MBF in the corresponding epicardial vessel segment increased from 0.76 +/- 0.16 to 1.03 +/- 0.33 mL x min(-1) x g(-1) (DeltaMBF, 0.27 +/- 0.25 mL x min(-1) x g(-1)) or 36% +/- 31% (P <or= 0.0001). However, in normal controls without coronary risk factors (n = 22), the epicardial LA increased from 5.01 +/- 1.07 to 5.88 +/- 0.89 mm(2) (19.06% +/- 8.9%) and MBF increased from 0.77 +/- 0.16 to 1.34 +/- 0.34 mL x min(-1) x g(-1) (74.08% +/- 23.5%) during CPT, whereas patients with coronary risk factors (n = 34) revealed a decrease of epicardial LA from 5.13 +/- 1.48 to 4.24 +/- 1.12 mm(2) (-15.94% +/- 12.2%) and a diminished MBF increase (from 0.76 +/- 0.20 to 0.83 +/- 0.25 mL x min(-1) x g(-1) or 10.91% +/- 19.8%) as compared with controls (P < 0.0001, respectively), despite comparable changes in the RPP (P = NS). In addition, there was a significant correlation (r = 0.87; P <or= 0.0001) between CPT-related percent changes in LA on quantitative angiography and in MBF as measured with PET. CONCLUSION: The observed close correlation between an angiographically established parameter of flow-dependent and, most likely, endothelium-mediated coronary vasomotion and PET-measured MBF further supports the validity and value of MBF responses to CPT as a noninvasively available index of coronary circulatory function.

An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28

[(11)C]PBR28 binds the 18-kDa Translocator Protein (TSPO) and is used in positron emission tomography (PET) to detect microglial activation. However, quantitative interpretations of signal are confounded by large interindividual variability in binding affinity, which displays a trimodal distribution compatible with a codominant genetic trait. Here, we tested directly for an underlying genetic mechanism to explain this. Binding affinity of PBR28 was measured in platelets isolated from 41 human subjects and tested for association with polymorphisms in TSPO and genes encoding other proteins in the TSPO complex. Complete agreement was observed between the TSPO Ala147Thr genotype and PBR28 binding affinity phenotype (P value=3.1 x 10(-13)). The TSPO Ala147Thr polymorphism predicts PBR28 binding affinity in human platelets. As all second-generation TSPO PET radioligands tested hitherto display a trimodal distribution in binding affinity analogous to PBR28, testing for this polymorphism may allow quantitative interpretation of TSPO PET studies with these radioligands.

Serial brain (18)FDG-PET in anti-AMPA receptor limbic encephalitis.

Immunotherapy-responsive autoimmune CNS syndromes linked to antibodies targeting surface neuronal antigens lack reliable biomarkers of disease activity. We report serial cerebral (18)FDG PET studies in a woman with AMPA receptor (AMPA-R) autoimmune limbic encephalitis. During her follow-up, despite an aggressive immunotherapy, she displayed a persistent, predominantly left hippocampal FDG hypermetabolism, in the absence of CNS inflammatory signs. Brain metabolism abnormalities regressed after increasing antiepileptic treatment, correlating with a moderate clinical improvement. Brain (18)F-FDG PET could thus represent a useful complementary tool to orient the clinical follow-up.

18F-fluorodeoxyglucose PET/CT findings in pleural effusions of patients with known cancer. A cytopathological correlation.

Aim: Pleural effusion is common in cancer patients and to determine its malignant origin is of huge clinical significance. PET/CT with 18F-FDG is of diagnostic value in staging and follow-up, but its ability to differentiate between malignant and benign effusions is not precisely known. Patients, methods: We examined 50 PET/CT from 47 patients (29 men, 18 women, 60±16 years) with pleural effusion and known cancer (24 NSCLC, 7 lymphomas, 5 breasts, 4 GIST, 3 mesotheliomas, 2 head and neck, 2 malignant teratoma, 1 colorectal, 1 oesophageal, 1 melanoma) for FDG uptake in the effusions using SUVmax. This was correlated to cytopathology performed after a median of 21 days (interquartile range -3 to 23), which included pH, relative distribution (macrophages, neutrophils, eosinophils, basophils, lymphocytes, plasmocytes), and absolute cell count. Results: Malignant cells were found in 17 effusions (34%) (6 NSCLC, 5 lymphomas, 2 breasts, 2 mesotheliomas, 2 malignant teratomas). SUV in malignant effusions were higher than in benign ones [3.7 (95%CI 1.8-5.6) vs. 1.7 g/ml (1.5-1.9), p = 0.001], with a correlation between malignant effusion and SUV (Spearman coefficient r = 0.50, p = 0.001), but not with other cytopathological or radiological parameters (ROC area 0.83±0.06). Using a 2.2-mg/l SUV threshold, 12 PET/CT studies were positive and 38 negative with sensitivity, specificity, positive and negative predictive values of 53%, 91%, 75% and 79%, respectively. For NSCLC only (n = 24), ROC area was 0.95±0.04, 7 studies were positive and 17 negative with a sensitivity, specificity, positive and negative predictive values of 83%, 89%, 71 and 94%, respectively. Conclusion: PET/CT may help to differentiate the malignant or benign origin of a pleural effusion with a high specificity in patients with known cancer, in particular NSCLC.

First imaging results of an intraindividual comparison of (11)C-acetate and (18)F-fluorocholine PET/CT in patients with prostate cancer at early biochemical first or second relapse after prostatectomy or radiotherapy.

PURPOSE: (18)F-Fluorocholine (FCH) and (11)C-acetate (ACE) PET are widely used for detection of recurrent prostate cancer (PC). We present the first results of a comparative, prospective PET/CT study of both tracers evaluated in the same patients presenting with recurrence and low PSA to compare the diagnostic information provided by the two tracers. METHODS: The study group comprised 23 patients studied for a rising PSA level after radical prostatectomy (RP, 7 patients, PSA ≤ 3 ng/ml), curative radiotherapy (RT, 7 patients, PSA ≤ 5 ng/ml) or RP and salvage RT (9 patients, PSA ≤ 5 ng/ml). Both FCH and ACE PET/CT scans were performed in a random sequence a median of 4 days (range 0 to 11 days) apart. FCH PET/CT was started at injection (307 ± 16 MBq) with a 10-min dynamic acquisition of the prostate bed, followed by a whole-body PET scan and late (45 min) imaging of the pelvis. ACE PET/CT was performed as a double whole-body PET scan starting 5 and 22 min after injection (994 ± 72 MBq), and a late view (45 min) of the prostate bed. PET/CT scans were blindly reviewed by two independent pairs of two experienced nuclear medicine physicians, discordant subgroup results being discussed to reach a consensus for positive, negative end equivocal results. RESULTS: PET results were concordant in 88 out of 92 local, regional and distant findings (Cohen's kappa 0.929). In particular, results were concordant in all patients concerning local status, bone metastases and distant findings. Lymph-node results were concordant in 19 patients and different in 4 patients. On a per-patient basis results were concordant in 22 of 23 patients (14 positive, 5 negative and 3 equivocal). In only one patient was ACE PET/CT positive for nodal metastases while FCH PET/CT was overall negative; interestingly, the ACE-positive and FCH-negative lymph nodes became positive in a second FCH PET/CT scan performed a few months later. CONCLUSION: Overall, ACE and FCH PET/CT showed excellent concordance, on both a per-lesion and a per-patient basis, suggesting that both tracers perform equally for recurrent prostate cancer staging.

Detection of an asymptomatic right-ventricle cardiac metastasis from a small-cell lung cancer by F-18-FDG PET/CT.

A right heart metastasis of a small-cell lung cancer was found on the whole-body F-fluoro-deoxy-glucose positron emission tomography/computed tomography (F-FDG-PET/CT) of a 69-year-old smoker investigated for a right pulmonary mass discovered on chest radiography after a fracture of the right humerus. The PET scan showed an increased FDG uptake by the mass in the right lung and an intense, atypical focal activity of the right ventricle strongly suggestive of a neoplastic process. CT-guided lung biopsy revealed a small-cell lung cancer and myocardial biopsy confirmed the presence of a cardiac metastasis. The patient was treated with six cycles of chemotherapy followed by radiation therapy, which included the heart lesion. At follow-up PET/CT 2 months after the end of treatment, the abnormal cardiac uptake had disappeared, whereas increased FDG uptake persisted in the pulmonary residual mass.

Peritoneal carcinomatosis due to ovarian cancer: comparison between MDCT, MRI and 18F-FDG PET/CT

Purpose: To compare MDCT, MRI and 18F-FDG PET/CT for the detection of peritoneal carcinomatosis due to ovarian cancerMethods and Materials: Fifteen women (mean age 65±) with clinical suspicion of ovarian cancer and peritoneal carcinomatosis underwent MDCT, MRI and 18F-FDG PET/CT, simultaneously and shortly performed before surgery (delay 8.1± days). According to the peritoneal cancer index nine abdominopelvic regions were defined. We applied four scores of lesion size on MDCT and MR images, while the maximal standard uptake value (SUVmax) was measured on 18F-FDG PET/CT. Three sites of lymphadenopathy and posterobasal pleural carcinomatosis were also analyzed. First, one radiologist blindly and separately read MDCT and MR images, while one nuclear physician blindly read PET/CT images grading each lesion according to four diagnostic certitudes. Secondly, all the images were reviewed jointly and compared with histopathology. Receiver operating characteristics (ROC) analysis was performed.Results: Peritoneal implants were proven in ten women (75%). Altogether, 228 abdominopelvic sites were compared. Sensitivity and specificity for MDCT was 90.2% and 90.6%, for MRI 93.5% and 86.3%, and for 18F-FDG PET/CT 92.7% and 95.7%, respectively. ROC area under the curve were 0.93 for MDCT and MRI, and 0.96 for 18F-FDG PET/CT respectively. No significant differences (p=0.11) were found between the three modalities.Conclusion: Although MRI revealed to be the most sensitive and 18F-FDG PET/CT the most specific modality, no significant differences were shown between the three techniques.

Osteolytic metastasis detected by F18-FDG PET in a patient with lung carcinoma

We present a 53-year-old man with a vocal cord paralysis observed as a primary manifestation of lung carcinoma. Tc-99m MDP whole body bone scan were performed and resulted a normal scintiscan. The bone scan does not revealed suspicious foci of uptake. The possibility of bone metastasis was taken into consideration. A whole body F18-FDG-PET scan showed intense uptake in the left upper lung corresponding to the primary tumor. A bronchial biopsy confirmed infiltration by small cell lung carcinoma (SCLC). SCLC is composed of poorly differentiated, rapidly growing cells with disease usually occurring centrally rather than peripherally. It metastasizes early. The whole-body F18-FDG-PET scan clearly demonstrated a focus of increased uptake in the second lumbar vertebral body suspicious for osteolytic metastasis. A lytic bone metastasis was confirmed by MRI. The patient then received therapy and underwent follow up abdominal CT. The scan showed blastic changes in the L2 vertebra suggesting response to treatment.