Thesis (D.Tech.: Radiography)-Dept. of Radiography, Durban Institute of Technology, 2006 xxiii, 166 leaves / The purpose of this study was to evaluate 99mTc- methoxyisobutylisonitrile (MIBI) imaging, in terms of sensitivity and specificity, for non invasively detecting extracutaneous involvement of Kaposi’s sarcoma (KS) and for differentiating pulmonary infection from malignancy in acquired immunodeficiency syndrome (AIDS) patients before and after treatment. Current investigations are invasive.

Bone is a remarkable multifunctional tissue with the ability to regenerate and remodel without generating any scar tissue. However, bone loss due to injury or diseases can be a great challenge and affect the patient significantly. Autologous bone grafting is commonly used throughout the world. Autograft both fills the void and is bone inductive, housing the particular cells that are needed for bone regeneration. However, a regenerative complement to autograft is of great interest as the use of biomaterials loaded with bioactive molecules can avoid donor site morbidity and the problem of a limited volume of material. Two such regenerative products that utilise bone morphogenetic protein (BMP)-7 and -2 have been used for more than a decade clinically. Unfortunately, several side effects have been reported, such as severe swelling due to inflammation and ectopic bone formation. Additionally, the products require open surgery and use of supra physiological doses of the BMPs due to poor localisation and retention of the growth factor. The purpose of this thesis was to harness the strong inductive capacity of the BMP-2 by optimising the carrier of this bioactive protein, thereby minimising the side effects that are associated with the clinical products and facilitating safe and localised bone regeneration. We focused on an injectable hyaluronan-based carrier developed through polymer chemistry at the University of Uppsala. The strategy was to use the body’s own regenerative pathway to stimulate and enhance bone healing in a manner similar to the natural bone-healing process. The hyaluronan-based carrier has a similar composition to the natural extracellular matrix and is degraded by resident enzymes. Earlier studies have shown improved properties when adding hydroxyapatite, a calcium phosphate that constitutes the inorganic part of the bone matrix. In Paper I, the aim was to improve the carrier by adding other forms of calcium phosphate. The results indicated that bone formation was enhanced when using nano-sized hydroxyapatite. In Paper II, we discovered the importance of crushing the material, thus enhancing permeability and enlarging the surface area. We wished to further develop the carrier system, but were lacking an animal model with relatively high throughput, facilitated access, paired data, and we were also committed to the 3Rs of refinement, reduction, and replacement. To meet these challenges, we developed and refined an animal model, and this is described in Paper III. In Paper IV, we sought to further optimise the biomaterial properties of the hydrogel through covalent bonding of bisphosphonates to the hyaluronan hydrogel. This resulted in exceptional retention of the growth factor BMP-2. In Paper V, SPECT/PET/µCT was combined as a tri-modal imaging method to allow visualisation of the biomaterial’s in situ action, in terms of drug retention, osteoblast activity and mineralisation. Finally, in Paper VI the correlation between existing in vitro results with in vivo outcomes was observed for an array of biomaterials. The study identified a surprisingly poor correlation between in vitro and in vivo assessment of biomaterials for osteogenesis.

A análise de imagens médicas auxiliada por computador permite a análise quantitativa das anormalidades e garante maior precisão diagnóstica. Esse tipo de análise é importante para medicina nuclear com Single Photon Emission Computed Tomography (SPECT), pois no grupo de dados tridimensionais de imagens, padrões sutis de anormalidades muitas vezes são importantes achados clínicos. Porém, as imagens podem sofrer interferência de artefatos de atenuação da emissão de fótons por partes moles corporais, o que reduz sua acurácia diagnóstica. Desde que se possuam parâmetros de atenuação computados em um modelo que permita a comparação com imagens de um dado paciente, a interferência dos artefatos pode ser corrigida com ganho na acurácia diagnóstica, sem a necessidade de utilização de técnicas de correção que aumentem a dose de exposição à radiação pelo paciente. A proposta desse estudo foi a criação de um atlas de cintilografia de perfusão miocárdica, que foi obtido a partir de imagens de indíviduos normais, e o desenvolvimento de um algoritmo computacional para a detecção de anormalidades perfusionais miocárdicas, através da comparação estatística dos modelos do atlas com imagens de pacientes. Métodos de corregistro de imagens de mesma modalidade e outras técnicas de processamento de imagens foram estudados e utilizados para a comparação das imagens dos pacientes com o modelo apropriado. Pela análise visual dos modelos, verificou-se a sua validade como imagem representativa de normalidade perfusional. Para avaliação da detecção, a situação dos segmentos miocárdicos (normal ou anormal) indicada pelo algoritmo de detecção foi comparada com a situação apontada no laudo obtido pela concordância de dois especialistas, de modo a se verificar as concordâncias e discordâncias da técnica em relação ao laudo e se obter a significância estatística. Com isso, verificou-se um índice de concordância positiva da técnica em relação ao laudo de aproximadamente 50%, de concordância negativa próxima a 82% e de concordância geral próxima a 68%. O teste exato de Fisher foi aplicado às tabelas de contingência, obtendo-se um valor de p bicaudal inferior a 0,0001, indicando uma probabilidade muito baixa de as concordâncias terem sido obtidas pelo acaso. Melhorias no algoritmo deverão ser implementadas e testes futuros com um padrão-ouro efetivo serão realizados para validação da técnica. / The computer-aided medical imaging analysis allows the quantitative analysis of abnormalities and enhances diagnostic accuracy. This type of analysis is important for nuclear medicine that uses Single Photon Emission Computed Tomography (SPECT), because in the group of three-dimensional data images, subtle patterns of abnormalities often are important clinical findings. However, images can suffer interference from attenuation artifacts of the emission of photons by soft parts of the body, which reduces their diagnostic accuracy. Since there are attenuation parameters computed in a template that allows for comparison with images of a given patient, the artifacts interference can be corrected with a gain in diagnostic accuracy, without the need of using correction techniques that increase the radiation exposure dose of the patient. The purpose of this study was to create an atlas of myocardial perfusion scintigraphy, which was obtained from images of normal individuals and the development of a computational algorithm for detection of myocardial perfusion abnormalities by statistical comparison of atlas templates with images of patients. Methods of image registration of same modality and other image processing techniques were studied and used for comparison of patient images with the appropriate template. By the visual analysis of the templates it was found its validity as a representative image of normal perfusion. For the detection evaluation, the situation of myocardial segments (normal or abnormal) indicated by the detection algorithm was compared with the situation indicated in the medical appraisal report obtained by agreement of two specialists in order to determine the agreement and disagreement of the technique regarding the medical appraisal report and obtaining the statistical significance. Thus, there was a positive agreement index of the technique regarding the medical appraisal report of approximately 50%, a negative agreement index close to 82% and a general agreement index near 68%. The Fisher exact test was applied to the contingency tables, yielding a two-sided p-value less than 0.0001, that indicates a very low probability of the agreements have been obtained by chance. Algorithm improvements should be implemented and further tests with an effective gold-standard will be conducted to validate the technique.

La tomographie d'émission monophotonique (TEMP) dédiée au petit animal est une technique d'imagerie nucléaire qui joue un rôle important en imagerie moléculaire. Les systèmes TEMP, à l'aide de collimateurs pinholes ou multi-pinholes, peuvent atteindre des résolutions spatiales submillimétriques et une haute sensibilité pour un petit champ de vue, ce qui est particulièrement attractif pour imager des souris. Une géométrie de collimation originale a été proposée, dans le cadre d'un projet, appelé SIGAHRS, piloté par la société Biospace. Ce collimateur présente des longueurs focales qui varient spatialement dans le plan transaxial et qui sont fixes dans le plan axial. Une haute résolution spatiale est recherchée au centre du champ de vue, avec un grand champ de vue et une haute sensibilité. Grâce aux simulations Monte Carlo, dont nous pouvons maîtriser tous les paramètres, nous avons étudié cette collimation originale que nous avons positionnée par rapport à un collimateur parallèle et un collimateur monofocal convergent. Afin de générer des données efficacement, nous avons développé un module multi-CPU/GPU qui utilise une technique de lancer de rayons dans le collimateur et qui nous a permis de gagner un facteur ~ 60 en temps de calcul, tout en conservant ~ 90 % du signal, pour l'isotope ⁹⁹^mTc (émettant à 140,5 keV), comparé à une simulation Monte Carlo classique. Cependant, cette approche néglige la pénétration septale et la diffusion dans le collimateur. Les données simulées ont ensuite été reconstruites avec l'algorithme OSEM. Nous avons développé quatre méthodes de projection (une projection simple (S-RT), une projection avec volume d'intersection (S-RT-IV), une projection avec calcul de l'angle solide (S-RT-SA) et une projection tenant compte de la profondeur d'interaction (S-RT-SA-D)). Nous avons aussi modélisé une PSF dans l'espace image, anisotrope et non-stationnaire, en nous inspirant de la littérature existante. Nous avons étudié le conditionnement de la matrice système pour chaque projecteur et collimateur, et nous avons comparé les images reconstruites pour chacun des collimateurs et pour chacun des projecteurs. Nous avons montré que le collimateur original proposé est le système le moins bien conditionné. Nous avons aussi montré que la modélisation de la PSF dans l'image ainsi que de la profondeur d'intéraction améliorent la qualité des images reconstruites ainsi que le recouvrement de contraste. Cependant, ces méthodes introduisent des artefacts de bord. Comparé aux systèmes existants, nous montrons que ce nouveau collimateur a un grand champ de vue (~ 70 mm dans le plan transaxial), avec une résolution de 1,0 mm dans le meilleur des cas, mais qu'il a une sensibilité relativement faible (1,32x10⁻² %). / Small animal single photon emission computed tomography (SPECT) is a nuclear medicine imaging technique that plays an important role in molecular imaging. SPECT systems using pinhole or multi-pinhole collimator can achieve submillimetric spatial resolution and high sensitivity in a small field of view, which is particularly appropriate for imaging mice. In our work, we studied a new collimator dedicated to small animal SPECT, in the context of a project called SIGAHRS, led by the Biospace company. In this collimator, focal lengths vary spatially in the transaxial plane and are fixed in the axial plane. This design aims at achieving high spatial resolution in the center of the field of view, with a large field of view and high sensitivity. Using Monte Carlo simulations, where all parameters can be controlled, we studied this new collimator geometry and compared it to a parallel collimator and a cone-beam collimator. To speed up the simulations, we developed a multi-CPU/GPU module that uses a technique of ray tracing. Using this approach, the acceleration factor was ~ 60 and we restored ~ 90 % of the signal for ⁹⁹^mTc (140.5 keV emission), compared to a classical Monte Carlo simulation. The 10 % difference is due to the fact that the multi-CPU/GPU module neglects the septal penetration and scatter in the collimator. We demonstrated that the data acquired with the new collimator could be reconstructed without artifact using an OSEM algorithm. We developed four forward projectors (simple projector (S-RT), projector accounting for the surface of the detecting pixel (S-RT-IV), projection modeling the solid angle (S-RT-SA) of the projection tube, and projector modeling the depth of interaction (S-RT-SA-D)). We also modeled the point spread function of the collimator in the image domain, using an anisotropic non-stationary function. To characterize the reconstruction, we studied the conditioning number of the system matrix for each projector and each collimator. We showed that the new collimator was more ill-conditioned than a parallel collimator or a cone-beam collimator. We showed that the image based PSF and the modeling of the depth of interaction improved the quality of the images, but edge artefacts were introduced when modeling the PSF in the image domain. Compared to existing systems, we showed that this new collimator has a large field of view (~ 70 mm in the transaxial plane) with a resolution of 1.0 mm in the best case but suffers from a relatively low sensitivity (1.32x10⁻² %).

Bone is a remarkable multifunctional tissue with the ability to regenerate and remodel without generating any scar tissue. However, bone loss due to injury or diseases can be a great challenge and affect the patient significantly. Transplanting bone graft from one site in the patient to the site of fracture or bone void, i.e. autologous bone grafting is commonly used throughout the world. The transplanted bone not only fills voids, but is also bone inductive, housing the particular cells that are needed for bone regeneration. Nevertheless, a regenerative complement to autograft is of great interest and importance because the benefits from an off-the-shelf product with as good of healing capacity as autograft will circumvent most of the drawbacks with autograft. With a regenerative-medicine approach, the use of biomaterials loaded with bioactive molecules can avoid donor site morbidity and the problem of limited volume of material. Two such regenerative products that utilize bone morphogenetic protein 7 and 2 have been used for more than a decade in the clinic. However, some severe side effects have been reported, such as severe swelling due to inflammation and ectopic bone formation. Additionally, the products require open surgery, use of supra physiological doses of the BMPs due to poor localization and retention of the growth factors. The purpose of this thesis was to harness the strong inductive capability of the BMP-2 by optimizing the carrier of this bioactive protein, thereby minimizing the side effects that are associated with the clinical products and facilitating safe and localized bone regeneration at the desired site. We focused on an injectable hyaluronan-based carrier. The strategy was to use the body’s own regenerative pathway to stimulate and enhance bone healing in a manner similar to the natural bone-healing process. The hyaluronan-based carrier has a similar composition to the natural extracellular matrix and is degraded by resident hyaluronidase enzymes. Earlier studies have shown a more controlled release and improved mechanical properties when adding a weight of 25 percent of hydroxyapatite, a calcium phosphate that constitutes the inorganic part of the bone matrix. In Paper I, the aim was to improve the carrier by adding other forms of calcium phosphate. The results indicated that the bone formation was enhanced when using nano-sized hydroxyapatite. We wished to further develop the carrier system but were lacking an animal model with high output and easy access. We also wanted to provide paired data and were committed to the 3 Rs of refinement, reduction and replacement. To meet these challenges, we developed and refined an animal model, and this is described in Paper II. In Paper III, we characterized and optimized the handling properties of the carrier. In Paper IV, we discovered the importance of crushing the material, thus enhancing permeability and enlarging the surface area. In Paper V, we sought to further optimize biomaterial properties of the hydrogel through covalently bonding of bisphosphonates to the hyaluronan hydrogel. The results demonstrated exceptional retention of the growth factor BMP-2. In Paper VI, the in vivo response related to the release of the growth factor was examined by combining a SPECT/PET/µCT imaging method to visualize both the retention of the drug, and the in-vivo response in terms of mineralization.

Laparoscopic operations are a common and popular way for abdominal procedures. They are usually performed by insufflation of carbon dioxide (CO2) into the abdominal cavity. However, insufflation of CO2 may interfere with cardiac and circulatory as well as respiratory functions. The CO2-pneumoperitoneum (PP) may cause hypercarbia and acidosis. The direct effects of CO2 and acidosis lead to decreased cardiac contractility, sensitization of the myocardium to arrhythmogenic effects of catecholamines and systemic vasodilatation. There may even be long-lasting post-operative effects on breathing control. The pneumoperitoneum may also cause several respiratory changes, e.g. decreased functional residual capacity (FRC) and vital capacity (VC), formation of atelectasis, reduced respiratory compliance and increased airway pressure. Still, arterial oxygenation is mostly maintained or even improved during PP. In view of the apparently contradictory results in respiratory mechanics and gas exchange, the present studies were performed to evaluate respiratory changes on gas exchange and ventilation-perfusion distributions during PP in a porcine model. It was demonstrated that atelectasis during anaesthesia and PP may be estimated by an increased arterial to endtidal PCO2-gradient (study I). Perfusion was redistributed away from dorsal, collapsed lung regions when PP was established. This resulted in a better ventilation-perfusion match (study II). Increasing abdominal pressure shifted blood flow more and more away from collapsed lung tissue, decreased pulmonary shunt and improved oxygenation from 8 to 16 mmHg PP, despite an increase of atelectasis formation (study III). CO2-PP enhanced the shift of blood flow towards better ventilated parts of the lung compared to Air-PP. Moreover, sodium natriumprusside worsened the ventilation-perfusion match even more and blunted the effects previously seen with carbon dioxide. CO2 should therefore be the mediator of enhancing HPV during PP. In conclusion, pneumoperitoneum with CO2 causes atelectasis with elimination of ventilation in the dependent lung regions. However, an efficient shift of blood flow away from collapsed, non-ventilated regions results in a better ventilation-perfusion matching and better oxygenation of blood than without PP. A prerequisite for the beneficial effect is the use of carbon dioxide for the abdominal inflation, since it enhances HPV.

A análise de imagens médicas auxiliada por computador permite a análise quantitativa das anormalidades e garante maior precisão diagnóstica. Esse tipo de análise é importante para medicina nuclear com Single Photon Emission Computed Tomography (SPECT), pois no grupo de dados tridimensionais de imagens, padrões sutis de anormalidades muitas vezes são importantes achados clínicos. Porém, as imagens podem sofrer interferência de artefatos de atenuação da emissão de fótons por partes moles corporais, o que reduz sua acurácia diagnóstica. Desde que se possuam parâmetros de atenuação computados em um modelo que permita a comparação com imagens de um dado paciente, a interferência dos artefatos pode ser corrigida com ganho na acurácia diagnóstica, sem a necessidade de utilização de técnicas de correção que aumentem a dose de exposição à radiação pelo paciente. A proposta desse estudo foi a criação de um atlas de cintilografia de perfusão miocárdica, que foi obtido a partir de imagens de indíviduos normais, e o desenvolvimento de um algoritmo computacional para a detecção de anormalidades perfusionais miocárdicas, através da comparação estatística dos modelos do atlas com imagens de pacientes. Métodos de corregistro de imagens de mesma modalidade e outras técnicas de processamento de imagens foram estudados e utilizados para a comparação das imagens dos pacientes com o modelo apropriado. Pela análise visual dos modelos, verificou-se a sua validade como imagem representativa de normalidade perfusional. Para avaliação da detecção, a situação dos segmentos miocárdicos (normal ou anormal) indicada pelo algoritmo de detecção foi comparada com a situação apontada no laudo obtido pela concordância de dois especialistas, de modo a se verificar as concordâncias e discordâncias da técnica em relação ao laudo e se obter a significância estatística. Com isso, verificou-se um índice de concordância positiva da técnica em relação ao laudo de aproximadamente 50%, de concordância negativa próxima a 82% e de concordância geral próxima a 68%. O teste exato de Fisher foi aplicado às tabelas de contingência, obtendo-se um valor de p bicaudal inferior a 0,0001, indicando uma probabilidade muito baixa de as concordâncias terem sido obtidas pelo acaso. Melhorias no algoritmo deverão ser implementadas e testes futuros com um padrão-ouro efetivo serão realizados para validação da técnica. / The computer-aided medical imaging analysis allows the quantitative analysis of abnormalities and enhances diagnostic accuracy. This type of analysis is important for nuclear medicine that uses Single Photon Emission Computed Tomography (SPECT), because in the group of three-dimensional data images, subtle patterns of abnormalities often are important clinical findings. However, images can suffer interference from attenuation artifacts of the emission of photons by soft parts of the body, which reduces their diagnostic accuracy. Since there are attenuation parameters computed in a template that allows for comparison with images of a given patient, the artifacts interference can be corrected with a gain in diagnostic accuracy, without the need of using correction techniques that increase the radiation exposure dose of the patient. The purpose of this study was to create an atlas of myocardial perfusion scintigraphy, which was obtained from images of normal individuals and the development of a computational algorithm for detection of myocardial perfusion abnormalities by statistical comparison of atlas templates with images of patients. Methods of image registration of same modality and other image processing techniques were studied and used for comparison of patient images with the appropriate template. By the visual analysis of the templates it was found its validity as a representative image of normal perfusion. For the detection evaluation, the situation of myocardial segments (normal or abnormal) indicated by the detection algorithm was compared with the situation indicated in the medical appraisal report obtained by agreement of two specialists in order to determine the agreement and disagreement of the technique regarding the medical appraisal report and obtaining the statistical significance. Thus, there was a positive agreement index of the technique regarding the medical appraisal report of approximately 50%, a negative agreement index close to 82% and a general agreement index near 68%. The Fisher exact test was applied to the contingency tables, yielding a two-sided p-value less than 0.0001, that indicates a very low probability of the agreements have been obtained by chance. Algorithm improvements should be implemented and further tests with an effective gold-standard will be conducted to validate the technique.

Le développement de plusieurs méthodes de reconstruction quantitatives dédiées à la Tomographie par Emission Mono Photonique du petit animal a été au cœur de cette thèse. Dans cette optique, une modélisation rigoureuse par simulation Monte Carlo du processus d’acquisition du système disponible, a été mise en place et validée. La modélisation matricielle combinée à l’algorithme de reconstruction itératif OS-EM, a permis la caractérisation des performances du système. Les valeurs de sensibilité et de résolution spatiale tomographique sont respectivement de 0,027% au centre du champ de vue et de 0,87 mm. Les limitations majeures des méthodes Monte Carlo nous ont conduit à développer une génération matricielle efficace et simplifiée des effets physiques occurrents dans le sujet. Mon approche, basée sur une décomposition de la matrice système, associée à une base de données pré-calculées, a démontré un temps acceptable pour un suivi quotidien (1h), conduisant à une reconstruction d’images personnalisée. Les approximations inhérentes à l’approche mise en place ont un impact modéré sur les valeurs des coefficients de recouvrement, une correction d’environ 10% ayant été obtenue. / My thesis focuses on the development of several quantitative reconstruction methods dedicated to small animal Single Photon Emission Computed Tomography. The latter is based on modeling the acquisition process of a 4-heads pinhole SPECT system using Monte Carlo simulations.The system matrix approach, combined with the OS-EM iterative reconstruction algorithm, enabled to characterize the system performances and to compare it to the state of the art. Sensitivity of about 0,027% in the center of the field of view combined with a tomographic spatial resolution of 0,87 mm were obtained.The major drawbacks of Monte Carlo methods led us to develop an efficient and simplified modeling of the physical effects occurring in the subject. My approach based on a system matrix decomposition, associated to a scatter pre-calculated database method, demonstrated an acceptable time for a daily imaging subject follow-up (1h), leading to a personalized imaging approach. The inherent approximations of the scatter pre-calculated approach have a moderate impact on the recovery coefficients results, nevertheless a correction of about 10% was achieved.

Thoracic surgical procedures require partial or complete airway separation and the opportunity to exclude one lung from ventilation (one-lung ventilation, OLV). OLV is commonly associated with profound pathophysiological changes that may affect the postoperative outcome. It is injurious in terms of increased mechanical stress including alveolar cell stretch and overdistension, shear forces secondary to repeated tidal collapse and reopening of alveolar units and compression of alveolar vessels. Ventilation and perfusion distribution may thus be affected during and after OLV. The present studies investigated the influence of OLV on ventilation and perfusion distribution, on the gas/tissue distribution and on the lung histomorphology in a pig model of thoracic surgery. Anaesthetised and mechanically ventilated piglets were examined. The ventilation and perfusion distribution within the lungs was assessed by single photon emission computed tomography. Computed tomography was used to establish the effects of OLV on dependent lung gas/tissue distribution. The pulmonary histopathology of pigs undergoing OLV and thoracic surgery was compared with that of two-lung ventilation (TLV) and spontaneous breathing. OLV induced hyperperfusion and significant V/Q mismatch in the ventilated lung persistent in the postoperative course. It increased cyclic tidal recruitment that was associated with a persistent increase of gas content in the ventilated lung. OLV and thoracic surgery as well resulted in alveolar damage.  In the present model of OLV and thoracic surgery, alveolar recruitment manoeuvre (ARM) and protective ventilation approach using low tidal volume preserved the ventilated lung density distribution and did not aggravate cyclic recruitment of alveoli in the ventilated lung. In conclusion, the present model established significant alveolar damage in response to OLV and thoracic surgery. Lung injury could be related to the profound pathophysiological consequences of OLV including hyperperfusion, ventilation/perfusion mismatch and increased tidal recruitment of lung tissue in the dependent, ventilated lung.  These mechanisms may contribute to the increased susceptibility for respiratory complications in patients undergoing thoracic surgery. A protective approach including sufficient ARM, application of PEEP, and the use of lower tidal volumes may prevent the ventilated lung from deleterious consequences of OLV.

La néoangiogenèse tumorale est un élément pronostique de l’évolution de nombreux cancers. L’intégrine alphaVbeta3 ainsi que la métalloprotéase matricielle 9 (MMP-9), sont des marqueurs de ce processus. Leur ciblage offre la perspective d’une information diagnostique pour la détection précoce, l’évaluation de l’agressivité de pathologies et la sélection de patients répondeurs aux nouvelles thérapies anti-angiogéniques. Dans ce contexte, notre travail s’attèle à mettre au point les techniques nécessaires à la caractérisation de radiotraceurs. Des modèles de tumeurs richement néovascularisées ont été sélectionnés : le mélanome malin et le gliome malin. Nous nous sommes dans un premier temps intéressés à la détection de l’intégrine alphaVbeta3. Un traceur technétié, le 99mTc-DTPA-bis-c(RGDfK) a servi de support à la validation de nos techniques d’analyse. Cette méthodologie d’évaluation a ensuite été adaptée à des projets collaboratifs. L’étude du 18F-ribofuranose-RGD est réalisée avec le Centre de Recherche en Cancérologie de Toulouse (INSERM UMR 1037) et l’Institut des Sciences Moléculaires (CNRS UMR 5255). Un radioligand de la MMP-9, l’111In- DOTA-F3B, fait l’objet d’un partenariat avec l’ARNA (ARN : Régulations Naturelle et Artificielle, INSERM UMR 869) et l’Institut Lumière Matière (CNRS UMR 5306). Le composé technétié a démontré une bonne affinité et spécificité pour alphaVbeta3. In vivo, chez l’animal, les radioligands technétiés et fluorés ont permis l’identification de tumeurs alphaVbeta3 positives. L’111In-DOTA-F3B a, quant à lui, permis la visualisation de tumeurs chez l’animal et sur coupes tissulaires. Ces traceurs constituent une piste intéressante pour l’imagerie de la néoangiogenèse tumorale. / Tumor neoangiogenesis is a predictive element of the evolution of numerous cancers. AlphaVbeta3 integrin and matrix metalloprotease 9 (MMP-9) are markers of tumor neoangiogenesis. Their targeting appears of great interest either for early detection, aggressiveness staging of the disease or for selection of responders to new-targeted therapies. In this context, our objective is to develop methodologies needed for radiotracers characterization. Tracers have been investigated in different tumor models for which vascularization is very important: melanoma and glioma. First of all 99mTc-DTPA-bis-c(RGDfK) has been assessed in our laboratory and helped us to develop analytical methods. These methodologies were used in different partnership, the evaluation of 18F-ribofuranose-RGD targeting alphaVbeta3 with INSERM UMR 1037 and CNRS UMR 5255, and 111In-DOTA-F3B for molecular imaging of MMP-9 with INSERM UMR 869 and CNRS UMR 5306.The technetium peptide has demonstrated good affinity and specificity for alphaVbeta3. In vivo analysis in mice showed that both tracers were able to identify some alphaVbeta3-positive tumors. 111In-DOTA-F3B allowed us to detect hMMP-9 positive tumors in mice and in tumor tissue sections. In conclusion, these tracers still require to be investigated but represent promising tracers for tumor neoangiogenesis.