Purpose: Hypoxia in colorectal cancer (CRC) and gastroesophageal cancer (GEC) decreases tumour responsiveness to radio and chemotherapy leading to cancer progression and poor prognosis. This is the first study to utilise [18F]FAZA hypoxia radiotracer in patients with CRC and GEC. Methods: Six patients (mean age 68±8 years, 2 males and 4 females) with CRC and 4 patients diagnosed with GEC (mean age 65 years, 3 males and 1 female) were included in the study. [18F]FAZA was synthesised at the John Mallard Scottish PET Centre. After injection with 370 MBq of [18F]FAZA, PET/CT images with 60 min dynamic scan were acquired. In addition, 15 min static scans 2 hr post injection were performed. 3D PET images were reconstructed iteratively using an ordered subset expectation maximization (OSEM) method and fused to the corresponding low-dose CT images. [18F]FAZA uptake parameters including maximum standard uptake value (SUVmax), tumour-to-muscle ratio (T/M), tumour-to-bowel ratio (T/B) and volume of interest (VOI) were measured. Results: 4 out 6 patients with CRC (66%) showed clear uptake of [18F]FAZA in the primary tumour. The mean tumour SUVmax was 2.2±0.91 (range 1.12 - 3.71). The tumour SUVmax was significantly higher compared with muscle and bowel (t(5) =3.11, P=0.03), (t(5) =3.08, P=0.03), respectively. However, tumour SUVmean didn't differ significantly compared with muscle and bowel (t(5) =2.41 , P=0.06), (t(5) =2.46 , P=0.06) respectively. The mean tumour to muscle ratio (T/M) ratio was 1.89±0.64 (range 1.10 - 2.87), while the mean tumour to normal bowel (T/B) was 1.92±0.64 (range 1.08 - 2.74). However, [18F]FAZA did not accumulate in any of the tumours found in patients with GEC. Conclusions: [18F]FAZA PET/CT imaging is suitable and feasible for detecting CRC hypoxic tumour regions with image quality that can be used in clinical practice.

Orientador: Alvaro Rodolfo De Pierro / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Matematica, Estatistica e Computação Cientifica / Made available in DSpace on 2018-08-14T01:15:10Z (GMT). No. of bitstreams: 1 HelouNeto_EliasSalomao_M.pdf: 1733678 bytes, checksum: 44e680915a74638897d279b1d09a007f (MD5) Previous issue date: 2005 / Resumo: O principal assunto desta dissertação é a teoria e prratica em metodos iterativos incrementais relaxados para reconstrução estatística de imagens em Tomografia por Emissão de Positrons - PET. Especial atenção é dedicada ao estudo teorico dos algoritmos, com a apresentação de resultados novos sobre convergência com o parâmetro de relaxação variando dentre as subiterações e sobre a regularidade da sequência gerada por tais algoritmos no caso específico da função de log-verossimilhança que surge em PET. Alem disso, uma comparação experimental entre a qualidade da imagem obtida com metodos relaxados e não relaxados é efetuada / Abstract: The main subject of this dissertation is the theory and practice in iterative incremental relaxed methods for statistical image reconstruction in Positron Emission Tomograpy | PET. Special atention is drawn to the theoretical study of the algorithms, with the presentation of new results concerning convergence with a relaxation parameter wich is allowed to vary within the subiterations and about the regularity of the sequence generated by such algorithms in the specific case of the log-likelihood function that arises in PET. Furthermore, an experimental comparsion is made to test the quality of the image obtained with relaxed methods against those generated by non-relaxed ones / Mestrado / Mestre em Matemática Aplicada

Single-photon emission computed tomography (SPECT) is a nuclear-medicine imaging technique that has been shown to provide clinically useful images of radionuclide distributions within the body. The problem of quantitative determination of tomographic activity images from a projection data set leads to a mathematical inverse problem which is formulated as an integral equation. The solution of this problem then depends on an accurate mathematical model as well as a reliable and efficient inversion algorithm. The effects of attenuation and Compton scatter within the body have been incorporated into the model in the hopes of providing a more physically realistic mathematical model. The attenuated Radon transform is the mathematical basis of SPECT. In this work, the case of constant attenuation is reviewed and a new proof of the Tretiak-Metz algorithm is presented. A space-domain version of the inverse attenuated Radon transform is derived. A special case of this transform that is applicable when the object is rotationally symmetric, the attenuated Abel transform is derived, and its inverse is found. A numerical algorithm for the implementation of the inverse attenuated Radon transform with constant attenuation is described and computer simulations are performed to demonstrate the results of the inversion procedure. With the use of the single-scatter approximation and an energy-windowed detector, the effects of Compton scatter are incorporated into the model. The data is then taken to be the sum of primary photons and single-scattered photons. The scattered photons are modeled by a scatter operator acting on the original activity distribution within the object where the operator consists of convolution with a given analytic kernel followed by a boundary cut-off operation. A solution is given by first applying the inverse attenuated Radon transform to the data set. This leads to a Fredholm integral equation to which a Neumann series solution is constructed. Again simulations are performed to validate the accuracy of the assumptions within the model as well as to numerically demonstrate the reconstruction procedure.

The dependence of tumour growth and metastasis on blood vessels makes tumour angiogenesis a rational target for therapy. Imaging of αvβ3 expression could potentially be used as a biomarker and an early indicator of efficacy of antiangiogenic treatments at a molecular level. Research efforts have mainly focused on the development of RGD-based radiolabelled αvβ3 inhibitors suitable for PET and SPECT imaging modalities that, owing to their high sensitivity, represent the most powerful tool for monitoring in vivo tumour angiogenesis. The aim of this multidisciplinary project was the design, synthesis and biological evaluation of novel αvβ3 ligands as molecular imaging probes. Three classes of integrin antagonists were designed: 1) triazole-based RGD mimetics that can be isotopically-labelled with tritium, fluorine and iodine radioisotopes by means of highly practical procedures, 2) RGD peptidomimetics incorporating the metabolically stable 2,2,2-trifluoroethylamine function as a peptide bond bioisostere and 3) RGD cyclopeptides conjugated with FDR, a novel prosthetic group allowing glycosylation and 18F-fluorination of aminooxy-functionalised molecules in one synthetic step. RGD-based strategies have also been used for selective tumour delivery of chemotherapeutic agents. A number of cytotoxic drugs have been conjugated to RGD peptides, providing experimental evidence that αvβ3 targeted chemotherapy strategies could be used as a powerful tool to reduce the toxicity and augment the therapeutic window of existing cytotoxic agents. In this work, we described the rational design of a novel targeted cytotoxic conjugate containing a triazole-based RGD peptidomimetic as tumour-homing motif of the potent antimitotic agent, paclitaxel. Preliminary in vitro studies were performed to assess the therapeutic potential of this targeted cytotoxic construct.

Thesis (MSc)--Stellenbosch University, 2003. / ENGLISH ABSTRACT: Planar bone scintigraphy is highly sensitive but it may not be sensitive enough to detect subtle lesions in complex bony structures such as the spine. The accurate anatomic localisation of lesions in regions such as this is also limited using planar images. Single Photon Emission Computed Tomography (SPECT) results in a higher lesion contrast resulting in an improved sensitivity for the detection of subtle lesions. SPECT also enables improved lesion localisation, often valuable in distinguishing benign from malignant disease in the spine. A number of previous studies have demonstrated that the addition of SPECT of the spine significantly enhances the value of bone scintigraphy for the detection of bone metastases compared to planar imaging alone. These studies were however not done in the African context where patients typically present with more advanced disease. In a retrospective study of 576 patients with known primary tumors sent to our institution for bone scintigraphy for the diagnosis of bone metastases, we evaluated 119 patients in whom both planar imaging and SPECT were obtained. The studies were graded for the probability of metastatic disease, and the number of spinal lesions was determined with and without SPECT. The influence of adding SPECT on the interpretation of the study was determined in terms of the reported probability of metastatic disease, the exclusion and confirmation of metastatic disease, the decisiveness of interpretation, and the number of spinal lesions. The addition of SPEeT resulted in a statistically significant change in the interpretation of studies, although the actual numbers of patients affected were relatively small. SPEeT resulted in a more decisive interpretation of bone scintigraphy. There was a significant increase in the number of spinal lesions detected after the addition of SPEeT. It was concluded that although the use of SPEeT is ideal, acceptable results could be achieved using planar imaging alone in this patient population. This is particularly relevant in the African context, where SPEeT is often unavailable or scarce and in great demand. / AFRIKAANSE OPSOMMING: Planare beenflikkergrafie is hoogs sensitief, maar moontlik nie sensitief genoeg om subtiele letsels in ingewikkelde beenstrukture soos die werwelkolom aan te toon nie. Akkurate anatomiese lokalisasie van letsels in die genoemde strukture is beperk wanneer slegs planare beelde gebruik word. Enkelfoton-uitstraling Rekenaartomografie (EFERT) lewer 'n hoër letsel kontras, wat 'n verbeterde sensitiwiteit vir die opsporing van subtiele letsels tot gevolg het. EFERT lei ook tot verbeterde letsel lokalisasie, wat dikwels van waarde is om onderskeid tussen benigne en maligne siekte in die werwelkolom te tref. Reeds met 'n aantal vorige studies is aangetoon dat die toevoeging van EFERT van die werwelkolom die waarde van beenflikkergrafie in die opsporing van beenmetastases beduidend verhoog bo dié van planare beelding alleenlik. Hierdie studies is egter nie in omstandighede eie aan Afrika gedoen nie, waar pasiënte kenmerkend met gevorderde siekte voordoen. In In terugskouende studie van 576 pasiënte met bekende primêre tumore, wat na ons instelling verwys is vir beenflikkergrafie om beenmetastases op te spoor, het ons 119 pasiënte, wat beide planare beelding en EFERT ondergaan het, ge-evalueer. Die studies is gegradeer volgens die waarskynlikheid vir metastatiese siekte, en die hoeveelheid werwelkolom letsels, met en sonder EFERT, is bepaal. Die invloed van EFERT op die vertolking van die studie is bepaal in terme van die waarskynlikheid van metastatiese siekte, die bevestiging en uitskakeling daarvan, die beslistheid van vertolking, en die hoeveelheid werwelkolom letsels. Die toevoeging van EFERT het tot 'n statisties beduidende verandering in die vertolking van studies gelei, alhoewel die werklike getal pasiënte wat hierdeur geraak is, relatief min was. EFERT het 'n meer besliste vertolking van beenflikkergrafie tot gevolg gehad. Daar was 'n beduidende toename in die hoeveelheid werwelkolom letsels wat opgespoor is na die toevoeging van EFERT. Daar is tot die slotsom gekom dat, alhoewel die gebruik van EFERT wenslik is, aanvaarbare resultate met slegs die gebruik van planare beelding in hierdie pasiënt bevolkingsgroep verkry kan word. Dit is veral van belang in Afrikaomstandighede, waar EFERT dikwels onbeskikbaar of skaars is, en ook in groot aanvraag is.

published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy

An improved method is introduced for prediction of local tumor control following lung stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) patients using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). A normalized background-corrected tumor maximum Standard Uptake Value (SUVcmax) is introduced using the mean uptake of adjacent aorta (SUVref), instead of the maximum uptake of lung tumor (SUVmax). This method minimizes the variations associated with SUVmax and objectively demonstrates a strong correlation between the low SUVcmax (< 2.5-3.0) and local control of post lung SBRT. The false positive rates of both SUVmax and SUVcmax increase with inclusion of early (<6 months) PET scans, therefore such inclusion is not recommended for assessing local tumor control of post lung SBRT. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2013.

We report here the development of a Lewis acid catalyzed method for the dehydrative coupling of cyclic alcohols and nitriles to form amides with retention of configuration. By contrast, the formation of amides by nitrile trapping of carbocations (Ritter reaction) usually affords racemic product. The present reaction was accomplished by first converting alcohol starting materials to their corresponding chlorosulfites in situ. Even after an extensive search, only copper (II) salts were able to produce the desired conversion of these chlorosulfites to amides though with low catalytic turnover. Improving the turnover without deteriorating the stereochemical outcome was eventually accomplished by a careful selection of the reagent addition sequence and through the removal of gaseous byproducts. This Ritter-like coupling reaction proceeds in good yields with secondary cyclic alcohols under mild conditions. The stereochemical outcome likely due to fast nucleophilic capture of a non-planar carbocations (hyperconjomers) stabilized by ring hyperconjugation. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

Molecular imaging of the human body is beginning to revolutionize drug development, drug delivery targeting, prognostics and diagnostics, and patient screening for clinical trials. The primary clinical tool of molecular imaging is Positron Emission Tomography (PET), which uses radioactively tagged probes (radioligands) for the in vivo quantification of blood flow, metabolism, protein distribution, gene expression and drug target occupancy. While many radioligands are used in human research, only a few have been adopted for clinical use. A major obstacle to translating these tools from bench-to-bedside is that PET images acquired using complex radioligands can not be properly interpreted or quantified without arterial blood sampling during the scan. Arterial blood sampling is an invasive, risky, costly, time consuming and uncomfortable procedure that deters subjects' participation and requires highly specialized medical staff presence and laboratories to run blood analysis. Many approaches have been developed over the years to reduce the number of blood samples for certain classes of radioligands, yet the ultimate goal of zero blood samples has remained illusive. In this dissertation we break this proverbial blood barrier and present for the first time a non-invasive PET quantification framework. To accomplish this, we introduce novel image processing, modeling, and tomographic reconstruction tools. First, we developed dedicated pharmacokinetic modeling, machine learning and optimization framework based on the fusion of Electronic Health Records (EHR) data with dynamic PET brain imaging information. EHR data is used to infer individualized metabolism and clearance rates of the radioligand from the body. This is combined with simultaneous estimation on multiple distinct regions of the PET image. A substantial part of this effort involved curating, and then mining, an extensive database of PET, EHR and arterial blood sampling data. Second, we outline a new tomographic reconstruction and resolution modeling approach that takes into account the scanner point spread function in order to improve the resolution of existing PET data-sets. This technique allows visualization and quantification of structures smaller than previously possible. Recovery of signal from blood vessels and integration with the non-invasive framework is demonstrated. We also show general applicability of this technique for visualization and signal recovery from the raphe, a sub-resolution cluster of nuclei in the brain that were previously not detectible with standard techniques. Our framework can be generalizable to all classes of radioligands, independent of their kinetics and distribution within body. Work presented in this thesis will allow the PET scientific and clinical community to advance towards the ultimate goal of making PET cost-effective and to enable new clinical use cases.

Orientador: Eloi Dezan Junior / Banca: Gustavo Sivieri de Araújo / Banca: Rodrigo Ricci Vivan / Resumo: Nódulos pulpares são calcificações presentes na câmara pulpar, aderidos nas paredes dentinárias ou como nódulos soltos e podem bloquear parcialmente ou totalmente o acesso aos orifícios dos canais radiculares. Devido à limitação de estudos realizados anteriormente com radiografias, o objetivo desse trabalho foi determinar a prevalência de nódulos pulpares por meio da tomografia computadorizada de feixe cônico (TCFC) e explorar qualquer correlação potencial entre a ocorrência de nódulos pulpares com gênero, idade, dente, arcada e estado da coroa dentária. Para isso foram utilizadas TCFC de 300 pacientes, totalizando 631 molares. Todos os molares foram analisados nos planos sagital, axial e coronal e, quando presentes, os nódulos pulpares foram identificados como uma massa redonda ou oval hiperdensa. Após tabulação dos dados, a análise estatística foi realizada através da aplicação de testes de qui-quadrado. De um total de 300 pacientes, os nódulos pulpares foram identificados em 35% e em 25.5% dos 631 molares analisados. A presença dos nódulos pulpares foi mais frequente no sexo feminino (41.1%) do que no masculino (27.7%) e nos indivíduos com idade acima de 80 anos. Os primeiros molares superiores exibiram a maior incidência de nódulos pulpares. Nenhuma diferença significativa foi observada quando os arcos maxilar e mandibular e os lados foram comparados. A presença de nódulos pulpares foi elevada em molares restaurados quando comparados aos dentes íntegros (P <0,05). A Tomog... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Pulp stones are calcifications present in the pulp chamber adhered to dentin walls or as loose nodules and can partially or totally block access to root canals entrance. Due to radiographic limitation of previous reports, the objective of this study was to determine the prevalence of pulp stones by cone beam computerized tomography (CBCT) and to explore any potential correlation between the occurrence of pulp stones with gender, age, tooth, arches and condition of the dental crown. CBCT of 300 patients were assessed, totaling 631 molars. All molars were analyzed in the sagittal, axial and coronal planes and, when present, pulp stones were identified as a round or oval hyperdense mass. After data tabulation, statistical analysis was performed using chi-square tests. Of a total of 300 patients, pulp stones were identified in 35% and in 25.5% of the 631 analyzed molars. The presence of pulp stones was most frequently found in females (41.1%) than in males (27.7%) and in individuals aged over 80 years. The first upper molars showed the highest incidence of pulp stones. No significant difference was observed when maxillary and mandibular arches were compared neither sides. The presence of pulp stones was higher in restored molars when compared to intact teeth (P <0.05). Cone Beam Computerized Tomography is an efficient resource for the diagnosis and location of pulp stones (Complete abstract electronic access below) / Mestre