Repeat 18F-FDG PET for monitoring neoadjuvant chemotherapy in patients with stage III non-small cell lung cancer

PURPOSE: The relevance of (18)F-FDG PET for staging non-small cell lung cancer (NSCLC), in particular for the detection of lymph node or distant metastases, has been shown in several studies. The value of FDG-PET for therapy monitoring in NSCLC, in contrast, has not yet been sufficiently analysed. Aim of this study was to evaluate FDG-PET for monitoring treatment response during and after neoadjuvant radiochemotherapy (NARCT) in advanced NSCLC. METHODS: Sixty-five patients with histologically proven NSCLC stage III initially underwent three FDG-PET investigations, during NARCT prior to initiating radiation, and post-NARCT. Changes of FDG-uptake in the primary tumour at two time-points during NARCT were analysed concerning their impact on long-term survival. RESULTS: The mean maximum FDG uptake (standardized uptake value, SUVmax) of the whole group decreased significantly during NARCT (SUVmax PET 1: 14.9+/-4.0, SUVmax PET 3: 5.5+/-2.4, p=0.004). The difference between initial FDG uptake (PET 1) and uptake after induction chemotherapy (PET 2) was found to be highly predictive for long-term survival patients which had a greater than 60% decreases in their SUV change had a significantly longer survival than those below this threshold (5-year-survival 60% versus 15%, p=0.0007). Patients who had a lower than 25% decrease in their SUV change had a 5-years-survival lower than 5%. Furthermore, the difference between initial FDG uptake (PET 1) and uptake after completion of the whole NARCT (PET 3) was predictive for survival when 75% was applied as cut-off (p=0.02). However, the level of significance was considerably lower. CONCLUSION: FDG-PET is suitable for therapy monitoring in patients with stage III NSCLC. The decrease of FDG uptake during induction chemotherapy is highly predictive for patient outcome.     

18F-FET PET differentiation of ring-enhancing brain lesions.

The aim of this study was to explore the differential diagnostic value of PET using the amino acid O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) in patients with newly diagnosed solitary intracerebral lesions showing ring enhancement on contrast-enhanced MRI. METHODS: (18)F-FET PET analyses were performed on 14 consecutive patients with intracerebral ring-enhancing lesions. Eleven of the patients were additionally studied with (18)F-FDG PET. In all patients, the main differential diagnosis after MRI was a malignant lesion, in particular glioblastoma multiforme, versus a benign lesion, in particular brain abscess. A malignant tumor was suspected for lesions showing increased (18)F-FET uptake on PET images with a mean lesion-to-brain ratio of at least 1.6 ((18)F-FET PET positive). A nonneoplastic lesion was suspected in cases of minimal or absent (18)F-FET uptake, with a mean lesion-to-brain ratio of less than 1.6 ((18)F-FET PET negative). Histologic diagnosis was obtained by serial biopsies in 13 of the 14 patients. One patient refused the biopsy, but follow-up indicated an abscess because his lesion regressed under antibiotic therapy. RESULTS: Histology and clinical follow-up showed high-grade malignant gliomas in 5 patients and nonneoplastic lesions in 9 patients. The findings of (18)F-FET PET were positive in all 5 glioma patients and in 3 of 9 patients with nonneoplastic lesions, including 2 patients with brain abscesses and 1 patient with a demyelinating lesion. The findings of (18)F-FDG PET were positive (mean lesion-to-gray matter ratio > or = 0.7) in 4 of 4 glioma patients and 3 of 7 patients with nonneoplastic lesions. CONCLUSION: Although (18)F-FET PET has been shown to be valuable for the diagnostic evaluation of brain tumors, our data indicate that, like (18)F-FDG PET, (18)F-FET PET has limited specificity in distinguishing between neoplastic and nonneoplastic ring-enhancing intracerebral lesions. Thus, histologic investigation of biopsy specimens remains mandatory to make this important differential diagnosis.     

Clinical and familial study of arrhythmogenic right ventricular cardiomyopathy

Objective　To explore the characteristics of arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods　Seven patients with arrhythmogenic right ventricular cardiomyopathy and 34 members of three families were studied. All patients and family members underwent history collection, clinical examination, electrocardiogram (ECG), two-dimensional echocardiography (2-DE) and a signal averaging electrocardiogram. Programmed ventricular stimulation was performed in five patients. Results　All patients and family members had normal morphologic characteristics and normal function of the left ventricular by 2-DE. Fourteen persons had abnormal findings indicating ARVC. Five had enlargement of the right ventricular with diffused hypocontractility, eight had thin and systolic bulging in the focal anterior wall with hypokinesia and one had bulging of the inferior wall. Twenty-five persons (seven patients and 18 family members) had abnormal findings in ECG. Positive ventricular late potential was recorded in 13 persons (six patients). Two to three monomorphic ventricular tachycardia (VT) with left bundle branch block (LBBB) configurations were induced in five patients. Ventricular fibrillation was induced in two patients during the electrophysiologic study (EPS). Five patients had very high pacing threshold and/or ineffective pacing in one or many regions of the right ventricle. Two members of one family died suddenly. One member was a dwarf with ARVC. Spontaneous VT with a left bundle branch block (LBBB) configuration was recorded in five patients, polymorphic VT with extremely short coupling interval in one, and premature ventricular complexes with LBBB configuration in 12 (six patients). Conclusion　Our familial study strongly suggests that ARVC may be a hereditary disease and it is helpful in the diagnosis and detection of ARVC. The most common manifestations were abnormal structure and function of the right ventricle and abnormal ECG of repolarization and ventricular arrhythmia which originates from the right ventricle.     

Correlation Between In Vivo Antipyrine Metabolite Formation and Theophylline Metabolism in Rats

Two model substrates for oxidative hepatic enzyme activity, viz. antipyrine (A) and theophylline (T), were given simultaneously to rats by iv administration. Blood concentrations of A and T were measured by a high-performance liquid chromatographic (HPLC) method. Urinary excretions of A, T, and the major metabolites arising from A—4-hydroxyantipyrine (OHA), norantipyrine (NORA), 3-hydroxymethylantipyrine (HMA), and 4,4-dihydroxyantipyrine (DOHA)—and from T—1-methyluric acid (1-MU) and 1,3-dimethyluric acid (1,3-DMU)—were also determined by HPLC. It was found that the pharmacokinetic parameters obtained after the simultaneous administration of A and T at relatively low dose levels (A, 5.0 mg; and T, 1.3 mg) were not different from those obtained after the separate administration of A or T at the same dose level. In order to investigate whether the metabolic pathways of A and T are mediated by the same or closely related forms of the cytochrome P-450 system, metabolic clearances of A (CL_A,M) and T (CL_T,M) and the clearances for production of their various metabolites, obtained in untreated rats and in rats pretreated with 3-methylcholanthrene (MC) or with MC followed by 9-hydroxyellipticine (E), were correlated. These two compounds are a selective cytochrome P-448 inducer and inhibitor, respectively. Strong correlations were found between CL_T,M and the clearances for production of OHA, NORA, and DOHA but not HMA. The best correlation, however, was observed between CL_T,M and CL_OHA, not only when all data points were taken into account (r = 0.99), but also in separate pretreatment groups (r ranging from 0.87 to 0.92). Moreover, the slopes of these correlation lines varied only slightly among groups, while the intercepts were not significantly different from zero. In the separate pretreatment groups, the correlation coefficients for the correlations between CL_T,M and the clearance for production of the other metabolites of A were considerably lower, while the slopes of the correlation lines varied substantially. Clearances for production of the metabolites of T were strongly correlated with each other (r = 0.99) and with CL_OHA (r = 0.95). It can be concluded that theophylline metabolism and formation of OHA are mediated by the same or very similar forms of cytochrome P-450, whereas formation of the other major metabolites of A is not or only partly. The study of the various pathways of metabolism after simultaneous administration of drugs is a powerful tool in the study of correlations in drug metabolism in vivo.     

Use of amino acid PET in the Diagnostic and Treatment Management of cerebral gliomas

Structural as well as functional imaging methods are of special importance in neurooncology. Improvements of radionuclide and magnetic resonance-based imaging modalities over the past decade have enabled clinicians to non-invasively assess the dynamics of disease-specific processes at the molecular level in patients with malignant gliomas. To date, a range of complementary imaging parameters have been established in the diagnostic work-up of patients with brain tumours. Magnetic resonance imaging (MRI) provides morphological information as well as functional information such as vascular permeability, cell density, tumour perfusion, and metabolic information by using magnetic resonance spectroscopy. The use of radiolabelled amino acids for positron emission tomography (PET) allows a better delineation of tumour margins and improves targeting of biopsy and radiotherapy, and planning surgery. In addition, amino acid imaging appears useful in distinguishing tumour recurrence from non-specific post-therapeutic scar tissue, in predicting prognosis in low-grade gliomas, and in monitoring metabolic response during treatment. Taken together, MRI and PET provide complementary information about tumour biology and activity, thereby resulting in an improved understanding of the kinetics of tumour growth and therefore allow new insights into the pathophysiology of malignant brain tumours. However, multimodal imaging studies comparing the value of amino acid PET and functional methods of MRI (e.?g., perfusion and diffusion weighted imaging) are needed. From these studies, surrogate MRI and PET imaging techniques need to be derived to gain complementary structural and functional information of brain tumours that can be placed into common clinical practice which will optimise the clinical management of patients with malignant gliomas.     

Tumor vascular signals in renal masses: detection with Doppler US

The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses.     

PET with O-(2-18F-Fluoroethyl)-L-Tyrosine in peripheral tumors: first clinical results.

O-(2-18F-Fluoroethyl)-L-Tyrosine (18F-FET) PET has shown promising results in brain tumor diagnosis. The aim of this prospective study was to evaluate 18F-FET PET in comparison with 18F-FDG PET in patients with peripheral tumors. METHODS: Forty-four consecutive patients with suspected malignant tumors underwent 18F-FET PET and 18F-FDG PET within 7 d. Whole-body PET studies were performed 1 h after intravenous injection of 370 MBq of 18F-FET or 18F-FDG. Six patients were excluded from the analysis because a malignant tumor could not be verified. In 38 patients (7 with colorectal cancer, 6 with pancreatic cancer, 9 with head-neck cancer, 4 with lymphomas, 3 with lung cancer, 3 with ovarian cancer, 4 with breast cancer, and 2 with prostatic cancer), 18F-FET PET and 18F-FDG PET were compared. RESULTS: 18F-FET was positive in only 13 of 38 patients (8 with head-neck cancer, 3 with breast cancer, and 2 with lung cancer), whereas 18F-FDG exhibited increased uptake in 37 of 38 patients. All squamous cell carcinomas were found to be 18F-FET-positive tumors (8 head-neck cancer and 2 lung cancer), whereas most adenocarcinomas were found to be 18F-FET-negative tumors. In patients with colorectal cancer, pancreatic cancer, ovarian cancer, prostatic cancer, and lymphomas, no increased 18F-FET uptake could be identified. All lesions that exhibited increased 18F-FET uptake also showed increased 18F-FDG uptake. No additional lesion was identified by 18F-FET PET but not by 18F-FDG PET. A subgroup analysis of patients with head-neck carcinomas allowed a better distinction between malignant and inflammatory tissues with 18F-FET than with 18F-FDG. CONCLUSION: 18F-FET is inferior to 18F-FDG as a PET tracer for general tumor diagnosis. Our preliminary results suggest rather selective uptake of 18F-FET in squamous cell carcinomas. Compared with 18F-FDG PET, 18F-FET PET may allow a better distinction between tumors and inflammatory tissues in patients with squamous cell carcinomas.     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.