Imagerie moléculaire nucléaire des paragangliomes

Paragangliomas (PGL) are relatively rare neural crest tumors originating in the adrenal medulla (usually called pheochromocytoma), chemoreceptors (i.e., carotid and aortic bodies) or autonomic ganglia. These tumors are highly vascular, usually benign and slow-growing. PGL may occur as sporadic or familial entities, the latter mostly in association with germline mutations of the succinate dehydrogenase (SDH) B, SDHC, SDHD, SDH5, von Hippel-Lindau (VHL), ret proto-oncogene (RET), neurofibromatosis 1 (NF1) (von Recklinghausen's disease), prolyl hydroxylase domain protein 2 (PHD2) genes and TMEM127. Molecular nuclear imaging has a central role in characterization of PGL and include: somatostatine receptor imaging (¹¹¹In, ⁶⁸Ga), MIBG scintigraphy (¹³¹I, ¹²³I), ¹⁸F-dihydroxyphenylalanine (¹⁸F-DOPA) positron emission tomography (PET), and ¹⁸F-deoxyglucose (¹⁸F-FDG) PET. The choice of the tracer is not yet fully established but the work-up of familial forms often require the combination of multiple approaches.     

Imagerie moléculaire de la maladie de Parkinson : données actuelles

During the last years, knowledge and concepts concerning Parkinson's disease and other parkinsonian syndromes have progressed: a concept of network pathology with different clinical presentations and evolutions, involving several neurotransmission pathways succeeeded the single dopaminergic lesion concept. Imaging also changed with the development of MRI. In this context, the aim of this work is to bring up-to-date methodology and clinical contribution of dopaminergic neuron imaging. Nigrostriatal neuron imaging (dopamine transporter imaging) contributes to diagnosis of Parkinson's disease and Lewy body dementia. Dopamine receptor imaging mainly helps in differential diagnosis of parkinsonian syndromes (Parkinson's disease and Parkinson plus syndromes). The ongoing development of dopaminergic, cholinergic, serotoninergic tracers and the recent emergence of amyloid plaques and neurofibrillary tangles imaging open perspectives for molecular imaging and care of neurodegenerative diseases.     

Variation de l'encombrement moléculaire de la ribonucléase dans différentes conditions de dénaturation

Treatments which denature ribonuclease (such as pH 12, performic acid oxidation, urea) affect the elution volume of this protein when fractionated on Sephadex G-100 columns. This altered behaviour of ribonuclease on Sephadex seems to be due to the effect of the above treatments on either the secondary or the tertiary structure and consequently the molecular size of ribonuclease. The results presented in this report suggest that the behaviour of proteins during gel filtration can be used as a criterion of the disorganization of their structure.     

Ganglion sentinelle et détection moléculaire du statut ganglionnaire

Sentinel lymph node (SLN) biopsy is the most used practice in breast cancer, in absence of clinical or radiological evidence of node metastasis for stage T0, T1 and T2 until 3 cm tumours. About 20,000 patients each year could benefit from a SLN biopsy in France. Nevertheless, the mean rate of second surgical procedure is of 10 to 17%. Two techniques (OSNA^® et GeneSearch?) are actually available in France. Their principle is based upon an intraoperative diagnosis of the presence or absence of metastasis in the SLN, using a rapid, quantitative, accurate molecular assay. The literature shows that those tests have the advantage of being more sensitive (frequently greater than 95%) than the classical techniques of frozen section diagnosis. The concordance with histopathological examination is high too (> 90%). For some of the patients, these techniques avoid a second surgery, reduce the cost of the management and shorten the initiation of treatment. In the future, this approach could become a standard.     

Apports de la biologie dans le diagnostic des démences

Since 2007, the combined dosage of three biomarkers in the cerebrospinal fluid has been considered an essential component of procedures to help establish a diagnosis of Alzheimer’s disease (AD). These biomarkers include total-Tau proteins, phosphorylated variants of Tau and amyloid-beta peptides. Their levels are altered early during the course of AD but they are not useful for a differential diagnosis of other dementing disorders. Perspectives therefore focus on finding plasmatic biomarkers and developing new biomarkers that would aid discrimination between dementing disorders.     

Imagerie moléculaire de la plaque d’athérome vulnérable. Évaluation préclinique et clinique de traceurs radioactifs

Atherosclerotic cardiovascular diseases (CVD) are the leading cause of mortality worldwide, accounting for greater than 19.10⁶ deaths annually. Despite major advances in the treatment of CVD, a high proportion of CVD victims die suddenly while being apparently healthy, the great majority of these accidents being due to the rupture or erosion of a vulnerable coronary atherosclerotic plaque. Indeed, an acute heart attack is the first symptom of atherosclerosis in as much as 50% of individuals with severe disease. A non-invasive imaging methodology allowing the early detection of vulnerable atherosclerosis in selected individuals prior to the occurrence of any symptom would therefore be of great public health benefit. Nuclear imaging could potentially allow the identification of vulnerable patients by non-invasive scintigraphic imaging following administration of a radiolabeled tracer. The development of radiolabeled probes that specifically bind to and allow the in vivo imaging of vulnerable atherosclerotic plaques is therefore the subject of intense ongoing experimental and clinical research. Radiotracers targeted at the inflammatory process seem particularly relevant and promising. Recently, macrophage targeting allowed the experimental in vivo detection of atherosclerosis using either SPECT or PET imaging. A few tracers have also been evaluated clinically. Targeting of apoptosis and macrophage metabolism both allowed the imaging of vulnerable atherosclerotic plaques in the carotid vessels of patients. However, nuclear imaging of vulnerable plaques at the level of the coronary arteries remains a challenging issue because of the small size of atherosclerotic lesions and of their vicinity with blood and the circulating tracer activity.     

Systématique moléculaire des Mélitées

The holarctic subfamily Melitaeinae of Nymphalid butterflies (old genus Melitaea Hbn.) has been split into various genera by morphological systematics, but this division has been debated. This work presents the results of a preliminary survey of European taxa using two types of molecular criteria: analysis of enzyme variation by electrophoresis (19 loci) and sequencing of a mtDNA fragment (ND1 gene). The information provided by both kinds of markers are largely congruent. The division of the subfamily into two monophyletic lines corresponding to the genera Euphyryas s. 1. and Melitaea s. l. is validated. The subsequent division of the former genus into two units, Eurodryas and Hypodryas is also confirmed by molecular criteria. Inside rhe old genus Melitaea, a monophyletic assemblage, corresponding to the ‘Mellicta group’ is disclosed, but the phylogeny of the other species of the group is confused. Uniting them in a ‘Didymaeformia group’ or in a genus Melitaea s. str. risks rhe generation of a paraphyletic assemblage. It remains to be determined whether or not these results are due to insufficient resolution, or whether they reflecr a real evolutionary pattern