No abstract available

No abstract available

[en] The tiatide (mercapto-acetyl-tri-glycine or MAG-3) is a Tc-labelled radiopharmaceutical currently used in renal functional exploration. However, its labelling does not reach always a pure radiochemical product. The different types of radioactive impurities (hydrophile, lipophile, colloids, reduced pertechnetate) have not all the same renal kinetics and can falsify the scintigraphic quantification of renal clearance, among others by a hepato-biliary fixation. Hence, it is useful for the nuclear physicians to know the radiochemical purity of the labeller injected in order to interpret better the values of renal clearance. We have compared the different available techniques allowing to make evident qualitatively and/or quantitatively the labelling impurities in tiatide. Our aim is to validate, in our working conditions the procedure utilising micro-columns described by National Commission of Radiopharmaceuticals. The thin-layer chromatography (TLC) (plates Merck RP18), currently used, allows separating the tiatide from reduced or hydrolyzed technetium and from free pertechnetate. The hydrophilic or lipophilic impurities are not distinguished among them. Different revealing techniques are available: quantification by the radiochromatography reader (Bioscan, autoradiography on sensible film or by grating plates and counting by a gamma counter. Secondly, we made use of fractioned elution on chromatographic micro-columns (Sep Pack C18) followed by a gamma counting which allows to distinguish the tiatide and the lipophilic and hydrophilic impurities (without discriminating the reduced pertechnetate and the colloids). Finally, by HPLC (column RP18, isocratic or with gradient elution) allows quantifying the tiatide and the different present impurities: reduced pertechnetate, lipophilic and hydrophilic impurities. In conclusion, the most suited technique of routine analysis of radiochemical purity of tiatide is the fractional elution on micro-column. The TLC seems to be inadequate for such a study. The HPLC remains the reference technique, indispensable in validating any other method

[en] The radio-pharmacist is competent and a legal licensee to realizing magistral preparations, defined in the book V of public health Code. We present here the case of a radiopharmaceutical drug prepared extemporary on a medical prescription, the labelling of BZM by iodine 123. The choice of this molecule is made after obtaining the indispensable pre-requisites (lack of noxiousness, teratogenicity, validation by pre-clinic studies, etc). The IBZM allows achieving the etiologic diagnosis of extra-pyramidal syndromes by scintigraphic visualisation of central D2 dopaminergic receptors. The magistral preparation of a radiopharmaceutical implies: (1). Identification of the row materials indispensable in warranting the labelling quality and innocuity of the final injected product. This is done by means of routine chemical reactions, described by France Pharmacopoeia or specifically established. Thus, all the row materials are tested and referenced prior to utilization. (2). The radio-labelling is effected in the day of the examination following a validated procedure: labelling of BZM by sodium iodate in buffer acid medium, extraction of formed IBZM by an organic solvent, purification of IBZM by HPCL, brought in injectable form by chromatographic passage (Sep Pack) and sterilizing filtration. (3). The test of final product is done prior to its injection by measuring the pH and co-elution by HPLC with the cool standard product. The IBZM is delivered providing its radiochemical purity is higher than 90%. A sterility test of preparation is effected a posteriori. The magistral preparation of IBZM allows neurological scintigraphic examinations, still unique in nuclear medicine. Other radiopharmaceuticals with cerebral use will be proposed to clinicians by radio-pharmacists. In all the these cases, the quality of injected labeller will be warranted by the same pharmaceutic approach

[en] New radiopharmaceuticals were developed to explore the pre- or post-synaptic slopes of the dopaminergic terminations. At present, their interest is recognized for the differential diagnosis of the extra-pyramidal syndromes. Other various applications in neurology and psychiatry are in view. On the pre-synaptic slope, implied in the Parkinson's disease, the dopamine carrier, able to be visualized due to its iodine derivatives of cocaine, is localized. The βCIT, which is presently the best known specificity-free derivative, has actually an equivalent affinity for the dopamine carrier and the serotonin carrier. Besides, its kinetic does not allow its imaging in the day of injection. We have developed and validated another derivative, the PE2I: N-(3-Iodoprop-(2E)-enyl) -2β-carbometoxy -3β-(4'-methyl-phenyl) nortropane which displays the properties required by kinetic and specificity. On the post-synaptic slope the type-D2 dopaminergic receptors were localized, which can be explored by means of (iodolisuride) ergolenes and benzamide derivatives (IBZM). These ligands have not an AMM yet, therefore their utilization may be approached by magistral preparation. The scintigraphy of the D2 receptors and dopamine carrier could be useful for the earlier diagnosis and the therapeutic surveillance of the neuro-degenerative decease. The coupling of the pre- and post-synaptic scintigraphies may be taken into consideration to augment diagnosis potentiality

[en] As mouse imaging has become more challenging in preclinical research, efforts have been made to develop dedicated PET systems. Although these systems are currently used for the study of Physio-pathologic murine models, they present some drawbacks for brain studies, including a low temporal resolution that limits the pharmacokinetic study of radiotracers. The aim of this study was to demonstrate the ability of a radiosensitive intracerebral probe to measure the binding of a radiotracer in the mouse brain in vivo. Methods: The potential of a probe 0.25 mm in diameter for pharmacokinetic studies was assessed.First, Monte Carlo simulations followed by experimental studies were used to evaluate the detection volume and sensitivity of the probe and its adequacy for the size of loci in the mouse brain. Second, ex vivo autoradiography of 5-hydroxytryptamine receptor 1A (5-HT1A) receptors in the mouse brain was performed with the PET radiotracer 2'-methoxy-phenyl-(N-2'-pyridinyl)-p-F-18-fluoro-benzamido-ethylpiperazine (F-18-MPPF). Finally, the binding kinetics of F-18-MPPF were measured in vivo in both the hippocampus and the cerebellum of mice. Results: Both the simulations and the experimental studies demonstrated the feasibility of using small probes to measure radioactive concentrations in specific regions of the mouse brain. Ex vivo autoradiography showed a heterogeneous distribution of F-18-MPPF consistent with the known distribution of 5-HT1A in the mouse brain. Finally, the time-activity curves obtained in vivo were reproducible and validated the capacity of the new probe to accurately measure F-18-MPPF kinetics in the mouse hippocampus. Conclusion: Our results demonstrate the ability of the tested radiosensitive intracerebral probe to monitor binding of PET radiotracers in anesthetized mice in vivo, with high temporal resolution suited for compartmental modeling. (authors)

[en] The advent of the molecular era has just generated a revolution in the development of new in vivo imaging techniques to examine the integrative functions of molecules, cells, organ systems and whole organisms. Molecular imaging constitutes a new tool allowing the biologist to characterize, repeatedly and non-invasively, a large number of experimental models developed in rodents. In order to monitor biological processes such as gene expression, normal development, metabolic alterations or medical treatment effects, several methodological and technological challenges have to be raised up. Developments are needed in chemistry to create new radiotracers or contrast agents, and in physic, to adapt the medical imaging techniques to the constraints of small animal investigations. ANIMAGE is a multimodal imaging platform to image the structure and function of systems using and developing different technologies such as autoradiography, ultrasounds, positron emission tomography (PET), X-ray computed tomography (CT), magnetic resonance imaging and spectroscopy (MRI/MRS). The first biological applications and results are presented

[en] Combined Laser Induced Ignition and Plasma Spectroscopy (LI2PS) has the potential to give the exact local composition of a mixture at the ignition point and at the ignition time. However, as different laser energies are required to ignite a particular mixture as function of space, the typical approach using two power meters to calibrate the plasma spectroscopy measurement is not well suited. Furthermore, LI2PS requires single shot measurements and therefore high accuracy. In this paper, a novel calibration scheme is presented for application of Laser Induced Plasma Spectroscopy (LIPS) to gaseous analyses. Numerical simulations of air spectra are used to show that species emission can be used directly from the broadband spectra to determine the plasma conditions. The ratio of nitrogen emission around 744 nm and around 870 nm is found to be a sensitive indication of temperature in the emission ranging from 700 to 890 nm. Comparisons with experimental spectra show identical tendencies and validate the findings of the simulations. This approach is used in a partially-premixed hydrogen-air burner. First, helium is used instead of hydrogen. After an explanation of timing issue related to LIPS, it is shown that the calibration required depends only on nitrogen excitation and nitrogen-hydrogen ratio, without the need to know the deposited power. Measurements of the fuel distribution as function of injection momentum and spatial localization are reported. To illustrate the use of such a single shot approach, combined laser ignition and plasma spectroscopy is proposed. In this case, the calibration is based on hydrogen excitation and hydrogen-oxygen and hydrogen-nitrogen ratio. Results obtained with LI2PS show that ignition is successful only for high power and relatively high hydrogen concentration compared to the local mean. It is expected that LI2PS will become an important tool when dealing with partially-premixed or diffusion flame ignition

[en] The aim of this study was to demonstrate the ability of a recently developed β⁺-range sensitive intracerebral probe (β-Microprobe) to measure the binding kinetics of [¹⁸F]MPPF, a well-documented 5-HT_1A serotoninergic receptor ligand, in the dorsal raphe nucleus (DRN) of the anaesthetised rat. This midbrain nucleus presents a high concentration of 5-HT_1A receptors known to be implicated in the effects of antidepressants. The difficulty confronting this study lay in the fact that the dimensions of the DRN are smaller than the detection volume of the β-Microprobe. In the first part of the study, we studied the feasibility of this measurement from a theoretical point of view by autoradiography and a Monte Carlo simulation. We determined the optimal β-Microprobe location close to the DRN and verified that this configuration allowed accurate determination of [¹⁸F]MPPF specific binding in the nucleus. In the second part of our study, we measured the in vivo time-concentration curves of [¹⁸F]MPPF binding in the DRN in comparison with the cerebellum. The specificity of [¹⁸F]MPPF binding in the DRN was confirmed by its displacement after non-labelled 5-HT_1Aantagonist injection (MPPF or WAY-100635). Moreover, we verified the feasibility of using β-Microprobe monitoring and simultaneous validation by microdialysis to study the effect of an increase in extracellular serotonin, induced by fenfluramine injection, on [ ¹⁸F]MPPF binding in the DRN. Our theoretical simulations, confirmed by our experimental results, demonstrate the ability of this new device to monitor in vivo the binding of [ ¹⁸F]MPPF in the DRN of anaesthetised rodents. (orig.)

[en] The investigation of neurophysiological mechanisms underlying the functional specificity of brain regions requires the development of technologies that are well adjusted to in vivo studies in small animals. An exciting challenge remains the combination of brain imaging and behavioural studies, which associates molecular processes of neuronal communications to their related actions. A pixelated intracerebral probe (PIXSIC) presents a novel strategy using a submillimetric probe for beta⁺ radiotracer detection based on a pixelated silicon diode that can be stereotaxically implanted in the brain region of interest. This fully autonomous detection system permits time-resolved high sensitivity measurements of radiotracers with additional imaging features in freely moving rats. An application-specific integrated circuit (ASIC) allows for parallel signal processing of each pixel and enables the wireless operation. All components of the detector were tested and characterized. The beta⁺ sensitivity of the system was determined with the probe dipped into radiotracer solutions. Monte Carlo simulations served to validate the experimental values and assess the contribution of gamma noise. Preliminary implantation tests on anaesthetized rats proved PIXSIC's functionality in brain tissue. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with high temporal resolution. (paper)