João José Pedroso de Lima

Silencing of phosphonate-gadolinium magnetic resonance imaging contrast by hydroxyapatite binding

Rationale and Objectives:GdDOTP5− is a highly charged, bone-seeking paramagnetic complex that could potentially detect bone lesions by magnetic resonance imaging (MRI). To date, its pharmacokinetics, effects on organ relaxivity, and interaction with hydroxyapatite (HA) has not been described. Methods:Liver, kidney, and bone MRI images were obtained on male white rabbits after the administration of GdDOTP5− or a gold standard MRI contrast agent, GdDTPA2−. Parallel in vitro experiments quantified the effect of HA binding on GdDOTP5− -induced changes in relaxivity. Results:The 2 compounds showed similar MRI enhancements in visceral tissues, but no enhancement of bone was evident with GdDOTP5− despite confirmation of bone and HA binding of the radioactive 153SmDOTP5− and 111InDOTP5− derivatives. In vitro experiments demonstrated that GdDOTP5−-induced changes in relaxivity were silenced upon HA binding but could be recovered by acid elution of the complex. Conclusions:HA binding assays revealed that GdDOTP5− is essentially MR silent when bound to bone, likely because of the exclusion of all outer sphere water molecules from the surface of the complex. These data suggest a novel strategy for creating highly sensitive, switchable MRI contrast agents.

Nanoradioliposomes molecularly modulated to study the lung deep lymphatic drainage

Abstract Lung deep lymphatic drainage (LDLD) plays an important role in the removal of foreign materials from lungs being alveolar macrophages the first line of phagocytic defence with high affinity for pathogenic microorganisms. Bacillus subtilis is a well-known genome- decoded saprophyte of the human respiratory tract used in research and in the biotechnology industry. Lung deep lymphatic chains (LDLC) constitute one of the first sites of lung tumours’ dissemination. In this work we intended to develop and validate a non-invasive method for assessing LDLC by nanoradioliposomes aerosolised modulated on the Bacillus subtilis spore wall. The final goal was to produce a nanoradioliposome formulation that can mimics the dynamics of preferential removal of spores by LDLD and present the ideal properties as a tracer for molecular imaging studies. Seven different liposomal formulations were tested, and the formulation-F demonstrated physicochemical and radiopharmaceutical properties that make it an ideal candidate as an in vivo probe for molecular imaging studies of the LDLC. Nanoradioliposomes of the formulation-F after labelling with 99mTc-HMPAO were administered as aerosols to 20 Sus scrofa. Hilar and interpulmonary communications were visualized in first 5 minutes post-inhalation, infradiaphragmatic chains between 10 and 20 minutes, the ganglia of the aortic chain at 20 minutes and those of the renal hilar region at 30 minutes. Conclusion the proposed method enables visualization of deep lymphatic lung network and lymph nodes. Besides, this technique involving the modulation of nanoradioliposomes targeting specific organs or tissues may be an important tool for diagnostic or even for therapeutic purposes.

Spiral cathode spark chambers for radiochromatography

Abstract This paper describes and discusses the performance of spark chambers which are designed to visualise the distribution of β-emitting radioactivity on chromatograms. The chambers comprise an assembly of individual detectors with spiral wire cathodes and concentric wire anodes. This design leads to ease of construction with good uniformity of sensitivity and stability of operation; sufficient for routine use in radiochromatography.

Radioisotopes in medicine

Radioisotopes are extensively used in medicine for diagnosis, either in vivo or in vitro, for therapeutics and also for investigation purposes. Nuclear medicine (NM) studies in vivo are used to detect minimal amounts of radiopharmaceuticals in organs (the morphology) and their course over time (the function), resulting from physico-chemical interactions of the tracers within the body, in the sequence of specific physiological processes. In vitro applications of radioisotopes have become a most important tool in biochemical analysis. Therapeutic uses of radioisotopes cover from external gamma-ray sources in teleradiotherapy to direct cell irradiation in metabolic therapy. The information, which is conveyed by NM, is essentially metabolic and differs from that supplied by the other imaging techniques, which is basically structural. This quality is important in early detection and diagnosis. Efforts have steadily been made to bring NM imaging as close as possible to an ideal medical diagnostic tool: non-invasive and allowing studies yielding functional, morphological, three-dimensional and quantitative information simultaneously. Of the two tomographic techniques available in NM, positron emission tomography (PET) is probably closer to this goal than single-photon emission tomography (SPECT). High-contrast functional images of the dynamics of labelled molecules (native or functionally similar) that are metabolized by the organs under investigation, are obtained with these techniques. Nuclear medicine has progressed as a result of advances in four strategic areas: the development of new radiopharmaceuticals, the technology and reliability of detectors, the capacity for modelling the metabolic fate of the inputs in the biological systems, and finally the ability to extract and process data.

Nanorradiolipossomas modulados molecularmente para estudar a drenagem linfática pulmonar profunda

Resumo A drenagem linfatica pulmonar profunda (DLPP) desempenha um papel importante na remocao de materiais estranhos, constituindo os macrofagos alveolares a primeira linha de defesa fagocitaria, dada a grande afinidade para microrganismos patogenicos. Os Bacillus subtilis sao saprofitas do tracto respiratorio humano com ampla utilizacao em investigacao e em biotecnologia. As cadeias linfaticas pulmonares profundas (CLPP) constituem um dos primeiros locais de disseminacao de tumores pulmonares. Neste trabalho pretendeu-se desenvolver e validar um metodo nao invasivo para avaliar as CLPP atraves de nanorradiolipossomas aerosolisados e modulados pela parede do esporo do Bacillus subtilis . O objectivo final foi produzir uma formulacao de nanorradiolipossomas capaz de imitar a dinâmica da remocao de esporos pelas CLPP e simultaneamente ter propriedades ideais como tracador para imagiologia molecular. Testamos sete diferentes formulacoes lipossomicas, tendo a formulacao F demonstrado possuir propriedades fisicoquimicas e radiofarmaceuticas que a tornam o tracador ideal para imagiologia molecular in vivo das CLPP. Os nanorradiolipossomas da formulacao F apos marcacao com 99m Tc-HMPAO foram administrados sob a forma de aerossois a 20 Sus scrofa . Visualizaram-se comunicacoes hilares e interpulmonares nos primeiros 5 minutos apos a inalacao, as cadeias infradiafragmaticas entre os 10 e os 20 minutos, os gânglios da cadeia aortica aos 20 minutos e os da regiao hilar renal aos 30 minutos. Em conclusao, o metodo proposto visualiza os gânglios linfaticos e a rede linfatica pulmonar profunda. A modulacao dos nanorradiolipossomas permite que eles atinjam orgaos ou tecidos especificos, conferindo-lhes importantes potencialidades no âmbito do diagnostico e/ou da terapeutica. Rev Port Pneumol 2009; XV (2): 261-293

Spurious events in spiral cathode spark chambers

Abstract The main difficulty in using spark chambers in routine laboratory applications such as autoradiography is the appearance of spurious sparks which are not associated with the passage of ionisation radiation through the gas of the detectors. This paper describes an investigation of the production of initiatory electrons from the cathode surfaces of detectors by field emission effects. Electron emission rates from cathode surfaces have been measured as a function of applied electric field, cathode material and spark frequency. The results show that emission rates are high enough to account for a significant proportion of spurious sparks. Other effects leading to ionisation in the gas will also contribute to the spurious sparking rate. Conclusions are drawn as to suitable materials for spark counter cathodes.

Validação do estudo da permeabilidade da barreira alvéolocapilar com 133Xe

ABSTRACT A preliminary review of physical concepts related with the solubility of inert gases in tissues and with the permeability of inert gases through the alveolar-capillary membrane in the context of this paper, is firstly presented. The solubility laws of gases in liquids and tissues, the concept of partial pressure of a gas in a tissue, the solubility and partition coefficients, the equilibrium of gases in the lungs, the gas diffusion through the capillary walls, etc., are brevely dealed with in this part of the work. The importance of a physiological method to study the alveolar-capillary barrier permeability with local information is emphasized. In the present paper the physiological and practical reasons which favour gas utilization, and particularly 133 Xe, instead of aerosols, to evaluate the alveolar-capillary barrier permeability are considered. A method to evaluate the disappearance times of 133 Xe activity and obtain parametric images is described. The advantages to display 133 Xe permeability images concomitantly with the ventilation and perfusion images and its interest is shown with some examples. General aspects of the use of 99m Tc-DTPA aerosols and CO classical spirometry with infra red analysis to study the alveolar-capiillary barrier permeability are considered. In a group of pacients, parametric images of the alveolar-capillary barrier permeability were obtained both with 133 Xe, using our technique and with the usual method of Nuclear Medicine using 99m Tc-DTPA aerosols. The disapearence times obtained by the two techniques are in general terms correlated, however, a considerably higher specificity is obseved in the case of 133 Xe. In a second group of patients the global mean disapearence times of 133 Xe, in the region of interest of the lungs, were compared with the CO diffusion times obtained with a convencional CO test. The agreement between the tests is very good in what concerns the ability to distinguish normal from abnormal, however, the local information offered by the 133 Xe technique was felt to be an information of great value in many situations. The results obtained, up to now, with 133 Xe indicate that the information provided may be a further step in the study of the alveolar-capillary barrier compromises, even in the early stages.