No / (137)Cs concentrations in ten species of foliose lichens collected within Tsukuba-city in August 2013 ranged from 1.7 to 35 kBq/kg. The relationships between (137)Cs in two dominant species, Dirinaria applanata and Physcia orientalis, and the air dose rate (muSv/h) at the sampling sites were investigated. (137)Cs in P. orientalis measured about 1 year after the Fukushima nuclear accident was correlated (r(2) = 0.80) more closely with the air dose rate than those measured after about 2 years (r(2) = 0.65), possibly demonstrating its continued value as a biomonitor to reflect ambient fall-out levels. In contrast, those of Dirinaria applanata were not correlated with the air dose rate in either year.

Surface functionalised silica materials have been prepared, followed by the extensive testing of their ability to remove metal ions from aqueous solutions. Modifications include ligand attachment and polymer grafting from the silica surface whilst the metals tested range from first row transition metals right through to the lanthanides and actinides. Characterisation of the materials produced has been of paramount importance for the understanding of the modification process and this is also extensively discussed. Atom transfer radical polymerisation (ATRP) has been used as the primary polymerisation method. Following polymerisation of 2-hydroxyethyl methacrylate (HEMA), post functionalisation was attempted. However, this was found to cause severe cross-linking and all attempts to attach ligands to this failed. Nonetheless, this process was transferred to grafting from silica surfaces and a novel approach to the characterisation of this material was implemented. (3-aminopropyl) triethoxysilane (APTES) was reacted with multiple forms of silica, primarily ZEOprep silica (average particle size 71.48 πm) and fumed silica (0.007 μm). This produced an amine coated surface to which 2-bromoisobutyryl bromide (BIBB) was attached, providing the required surface for radical polymerisation to proceed with a selected monomer. Solid State Nuclear Magnetic Resonance (SSNMR) has been utilised as the major characterisation technique for each step, leading to significant understanding of how this occurs. Thermogravimetric Analysis (TGA) and elemental analysis has supported this method at each stage whilst also enabling one to calculate the moles of APTES present, per gram of APTES-functionalised silica. For the ZEOprep silica this was calculated to be at up to 1.51 x 10-3 mol g-1 and for the fumed silica 1.63 x 10-3 mol g-1. As well as testing the selective nature of these materials, solutions of individual ions and radionuclides were used to measure the effectiveness of the materials for a specific ion. Rd values for these metals ions including solutions of Co(II), Ni(II), Cu(II), Cd2+, Eu(III) and [UO2]2+ have reached values ranging from 7.49 x 104 mL g-1 to as high as 2.17 x 109 mL g-1. These values are regarded as outstanding by other groups that have reported similar results and these are discussed in the report. This range includes values that were observed when competing Na+ and Ca2+ ions were present at 0.5 % and 1 % (w/w). pH testing was also investigated with the materials using a solution of europium ions to determine the most effective range and this was found to fall between pH 4 and 5. X-ray Photoelectron Spectroscopy (XPS) has been utilised to help gain an understanding of the binding between Cu(II) ions and APTES, suggesting that copper ions bind with oxygen atoms closer to the silica surface as well as the nitrogen atoms at the end of the ligand. Meanwhile STEM (Scanning Transmission Electron Microscope) has been used to show how effectively the surface area of the material is used by imaging the europium ions over a sample of APTES-functionalised fumed silica. Ligands and polymers have been focussed on to build a catalogue of functional materials and this has been achieved in collaboration with PhosphonicS Ltd. The most significant finding from these selective investigations was that uranyl ions were found to be the most readily removed. Cu(II) and Eu(III) ions were also removed relatively effectively whilst Co(II), Ni(II), Zn2+ and Cd2+ proved the most challenging but certainly not impossible. [UO2]2+ concentrations were reduced from 17.1 ppm to 1.6 ppm after 4 weeks with use of the ligand SEA (2-aminoethyl sulfide ethyl silica), even with six other metal ions present at similar initial concentrations and a starting pH of 4.67 by adding just 50 mg of the material to a 45 mL solution.

The most promising applications for targeted alpha-therapy with astatine-211 (At-211) include treatments of disseminated microscopic disease, the major medical problem for cancer treatment. The primary advantages of targeted alpha-therapy with At-211 are that the alpha-particle radiation is densely ionizing, translating to high relative biological effectiveness (RBE), and short-range, minimizing damage to surrounding healthy tissues. In addition, theranostic imaging with I-123 surrogates has shown promise for developing new therapies with At-211 and translating them to the clinic. Currently, Canada does not have a way of producing At-211 by conventional methods because it lacks alpha-particle accelerators with necessary beam energy and intensity. The work presented here was aimed at studying the Rn-211/At-211 generator system as an alternative production strategy by leveraging TRIUMF's ability to produce rare isotopes. Recognizing that TRIUMF provided production opportunities for a variety of astatine isotopes, this work also originally hypothesized and evaluated the use of At-209 as a novel isotope for preclinical Single Photon Emission Computed Tomography (SPECT) with applications to At-211 therapy research. At TRIUMF's Isotope Separator and Accelerator (ISAC) facility, mass separated ion beams of short­-lived francium isotopes were implanted into NaCl targets where Rn-211 or At-209 were produced by radioactive decay, in situ. This effort required methodological developments for safely relocating the implanted radioactivity to the radiochemistry laboratory for recovery in solution. For multiple production runs, Rn-211 was quantitatively transferred from solid NaCl to solution (dodecane) from which At-211 was efficiently extracted and evaluated for clinical applicability. This validated the use of dodecane for capturing Rn-211 as an elegant approach to storing and shipping Rn-211/At-211 in the future. Po-207 contamination (also produced by Rn-211 decay) was removed using a granular tellurium (Te) column before proceeding with biomolecule labelling. Although the produced quantities were small, the pure At-211 samples demonstrated these efforts to have a clear path of translation to animal studies. For the first time in history, SPECT/CT was evaluated for measuring At-209 radioactivity distributions using high energy collimation. The spectrum detected for At-209 by the SPECT camera presented several photopeaks (energy windows) for reconstruction. The 77-90 Po X­-ray photopeak reconstructions were found to provide the best images overall, in terms of resolution/contrast and uniformity. Collectively, these experiments helped establish guidelines for determining the optimal injected radioactivity, depending on scan parameters. Moreover, At-209-based SPECT demonstrated potential for pursuing image-­based dosimetry in mouse tumour models, in the future. Simultaneous SPECT imaging with At-209 and I-123 was demonstrated to be feasible, supporting the future evaluation of At-209 for studying/validating I-123 surrogates for clinical image-based At-211 dosimetry. This work also pursued a novel strategy for labelling cancer targeting peptides with At-211, using octreotate (TATE, a somatostatin analogue for targeting tumour cells, mostly neuroendocrine tumours) prepared with or without N-terminus PEGylation (PEG2), followed by conjugation with a closo-decaborate linking moiety (B10) for attaching At-211. Binding affinity and in vivo biodistributions for the modified peptides were determined using iodine surrogates. The results indicated that B10-PEG2-TATE retained target binding affinity but that the labelling reaction with iodine degraded this binding affinity significantly, and although having high in vivo stability, no I-123-B10-PEG2-TATE tumour uptake was observed by SPECT in a mouse tumour model positive for the somatostatin receptor (sstr2a). This suggested that further improvements are required for labelling. A new method for producing At-211 at TRIUMF is established, and At-209-­based SPECT imaging is now demonstrated as a new preclinical technology to measure astatine biodistributions in vivo for developing new radiopharmaceuticals with At-211. Combined with the theranostic peptide labelling efforts with iodine, these efforts provide a foundation for future endeavours with At-211-­based alpha-therapy at TRIUMF. All procedures were performed safely and rapidly, suitable for preclinical evaluations. All animal studies received institutional ethics approval from the University of British Columbia (UBC). / Graduate

La thérapie de resynchronisation cardiaque (CRT) est un traitement qui vise à rétablir le synchronisme de contraction du ventricule gauche chez les patients souffrant d’insuffisance cardiaque. Aujourd’hui encore, plus de 30% de ces patients ne répondent pas au traitement de resynchronisation. Afin de mieux comprendre les effets de la CRT sur la fonction cardiaque, un resynchronisateur biventriculaire a été implanté chez des chiens sains et des chiens atteints d’insuffisance cardiaque. Les fonctions ventriculaires gauche et droite ont été étudiées selon différents modes de resynchronisation. Les résultats de cette étude confirment premièrement que la durée du complexe QRS n’est pas un marqueur approprié dans l’optimisation de la CRT. Les résultats démontrent également qu’une optimisation individualisée de la CRT est nécessaire afin de maximiser l’effet de la thérapie sur le ventricule gauche et que la modulation du délai de resynchronisation a un impact significatif sur la fonction ventriculaire droite. Plus précisément, la fonction systolique du ventricule droit est optimale lors d’une activation précoce de l’électrode gauche. / Cardiac resynchronization therapy (CRT) was introduced to reestablish the synchronism in left ventricular of heart failure patients. At the present time, more than 30% of these patients do not respond to the resynchronization treatments. In order to better understand the effect of CRT on the cardiac function, a biventricular pacemaker was implanted in healthy dogs and in dogs with induced heart failure. Results from this study show that using the QRS duration in order to optimize CRT is not recommended. In addition, they confirm that an individualized optimization of the CRT is necessary to maximize the effect of the therapy on the left ventricle and that the modulation of the resynchronization delay has a significant impact on the right ventricular function. More precisely, right ventricular systolic function is optimal with an early activation of the left electrode.

La fraction d’éjection du ventricule gauche est un excellent marqueur de la fonction cardiaque. Plusieurs techniques invasives ou non sont utilisées pour son calcul : l’angiographie, l’échocardiographie, la résonnance magnétique nucléaire cardiaque, le scanner cardiaque, la ventriculographie radioisotopique et l’étude de perfusion myocardique en médecine nucléaire. Plus de 40 ans de publications scientifiques encensent la ventriculographie radioisotopique pour sa rapidité d’exécution, sa disponibilité, son faible coût et sa reproductibilité intra-observateur et inter-observateur. La fraction d’éjection du ventricule gauche a été calculée chez 47 patients à deux reprises, par deux technologues, sur deux acquisitions distinctes selon trois méthodes : manuelle, automatique et semi-automatique. Les méthodes automatique et semi-automatique montrent dans l’ensemble une meilleure reproductibilité, une plus petite erreur standard de mesure et une plus petite différence minimale détectable. La méthode manuelle quant à elle fournit un résultat systématiquement et significativement inférieur aux deux autres méthodes. C’est la seule technique qui a montré une différence significative lors de l’analyse intra-observateur. Son erreur standard de mesure est de 40 à 50 % plus importante qu’avec les autres techniques, tout comme l’est sa différence minimale détectable. Bien que les trois méthodes soient d’excellentes techniques reproductibles pour l’évaluation de la fraction d’éjection du ventricule gauche, les estimations de la fiabilité des méthodes automatique et semi-automatique sont supérieures à celles de la méthode manuelle. / Left ventricular ejection fraction is an excellent indicator of cardiac function. Many invasive and non-invasive techniques can be used for its assessment: angiography, echocardiography, cardiac MRI, computed tomography of the heart, multigated radionuclide angiography and myocardial perfusion imaging. More than 40 years of scientific publication praise the multigated radionuclide angiography for its execution speed, its availability, its low cost and intrarater and interrater reproducibility. The left ventricular ejection fraction was calculated twice for 47 patients, using two raw data acquisitions, two technologists and three software platforms: one fully manual, one semi-automatic and one fully automatic. In general, the automatic and semi-automatic methods showed greater reproducibility, a smaller standard error of measurement and minimal detectable change than the manual method, whereas the manual method systematically gave a significantly lower quality of result. It was the only technique that showed significant intrarater difference, and its standard error of measurement and minimal detectable change were 40% to 50% higher than those of automatic and semi-automatic methods. Even though all three techniques are all excellent and reliable options, reliability coefficient estimations were superior using automatic and semi-automatic methods as compared to the manual method.

A doença cardiovascular (DCV) é uma condição clínica comum entre pacientes (pcts) portadores de doença renal crônica (DRC) e é causa de eventos fatais observados peri transplante renal (TX). A melhor estratégia de avaliação cardiovascular em candidatos a transplante (CTR) ainda é controversa.Ignora-se se todos os pacientes devem ser submetidos a testes não-invasivos/invasivos ou se estes devem ser reservados aqueles com determinadas características clínicas, como população geral. O objetivo deste estudo foi comparar a estratificação de risco baseada em método nãoinvasivo de detecção de doença coronária com dois métodos de estratificação clínica de risco cardiovascular preconizados pela American Society of Transplantation (AST) e European Renal Association (ERA). A AST subdivide os pcts em : alto risco (idade maior ou igual a 50 anos e/ou diabete e/ou DCV clínica) e baixo risco (os demais). A ERA subdivide em: alto risco (DCV clínica), risco intermediário (diabéticos e/ou idade maior ou igual a 50 anos) e baixo risco (os demais). Nós estudamos 386 pcts com DRC em diálise enviados ao nosso serviço para avaliação cardiovascular antes da inclusão na lista de espera de TX. Foram estratificados quanto ao risco de eventos de acordo com os dois algoritmos acima e alterações na cintilografia de perfusão miocárdica (SPECT-MIBI) com dipiridamol e acompanhados até a morte, TX ou ocorrência de eventos. A estratificação clínica (RR:1,8 [IC95% 1,3 2,6- P<0,0001] e o SPECT-MIBI (RR:1,5 [IC95% 1,2-1,9-P=0,002] identificaram os pcts de maior risco de eventos cardiovasculares . Apenas os pcts ASTalto risco (RR1,4 [IC95%1,1-1,8-P=0,002] e ERA médio risco com SPECTMIBI alterado (RR:1,7 [IC95% 1,2-2,3-P=0,003] tiveram maior incidência de eventos. Os pcts de baixo risco pelos dois algorítmos de estratificação clínica (P=0,50) e do sistema ERA alto risco (RR:1,1 [IC95% 0,8-1,5-P=0,41], não se beneficiaram dos resultados do estudo não-invasivo. Concluímos que os estudos não-invasivos não devem ser utilizados em todos os CTR mas devem ser reservados aos pcts previamente identificados pela estratificação clínica de risco. Esses resultados permitem uma abordagem mais racional da avaliação pré- TX com melhor uso dos recursos econômicos escassos. / Cardiovascular (CV) disease is a common condition in chronic kidney disease (CKD) patients and is the leading cause of fatal events during and after renal transplantation. The best strategy for CV evaluation and coronary risk stratification in renal transplant candidates remains controversial. Moreover, there is no consensus regarding the best strategy for detection of coronary artery disease (CAD). We still do not know if all patients should be evaluated by noninvasive testing or if this approach should be restricted to individuals with clinical evidence of CAD, as in the general population. The objective of this study was to compare CV risk stratification based on nonivasive testing for CAD with two clinical stratification methods as advanced by The American Society of Transplantation (AST) and by The European Renal Association (ERA), respectively. The AST divides patients in high risk (age50 years and/or diabetes and/or CV disease) and low risk (all others).The ERA divides : high risk (CV disease), intermediate risk (age 50 years and/or diabetes), and low risk (as above). We studied 386 CKD patients treated by hemodyalisis, to CV evaluation before being admitted to the renal transplant waiting list. All patients were stratified for the risk of future major cardiovascular events (MACE) using the clinical algorithms and also by myocardial scintigraphy (SPECT-MIBI) with dipyridamol and followedup until death, transplant or MACE. Clinical algorithms (RR:1,8 [IC95% 1,3 2,6-P<0,0001] and SPECT-MIBI(RR:1,5 [IC95% 1,2-1,9-P=0,002] identified patients at increased risk of events. The combined use of clinical stratification followed by SPECT showed that the only patients that would benefit from SPECT risk stratification were those belonging the AST-high risk (RR1,4 [IC95%1,1-1,8-P=0,002] and ERA-intermediate risk groups (RR:1,7 [IC95% 1,2-2,3-P=0,003]. In all other groups :ERA-high-risk (RR:1,1[IC95% 0,8-1,5- P=0,41] and ERA and AST-low-risk (P=0,50) SPECT did not add to the probability of events defined by clinical stratification alone. We conclude that SPECT should not be applied to all renal transplant candidates but should be restricted to those considered at a category of risk as defined by clinical algorithms. These results delineate a more rational approach to risk stratification in renal transplant candidates with a better utilization of economical resources.

Pacientes com diagnósticos oncológicos diversos sob terapia com agentes nefrotóxicos, foram avaliados através de procedimentos radioisotópicos, em três momentos diferentes. Os achados radioisotópicos foram comparados com as avaliações laboratoriais rotineiras. Não mostraram alterações estatisticamente significativas os seguintes parâmetros: uréia, creatinina, sedimentos anormais e índice de Crockoft-Gault. Concluiu-se que a avaliação da função renal com os métodos rotineiramente utilizados na prática oncológica não foram estatisticamente significativas. Dentre os estudos utilizando radionuclídeos, o DTPA-99mTc e DMSA-99mTc, evidenciaram alterações, enquanto o EC-99mTc, não as detectou / Patients with different oncologic diagnoses under treatment with nephrotoxic drugs were evaluated by radioisotopic agents at three different moments. Radioisotopic data were compared with biochemical routine tests. Concerning laboratorial parameters like serum creatinine, urea and Cockroft Gault index, no statistically significant changes were observed. Possible to conclude that renal function evaluation with methods routinely used in oncological practice did not reveal any statistically significant change. Radioisotopic studies using 99mTc-DTPA and 99mTc-DMSA showed considerable alterations, however with 99mTc-EC no significant changes were evidenced

I NTRODUÇÃO: Na cintilografia de perfusão do miocárdio, contrariamente ao desenvolvimento tecnológico ao longo do tempo, manteve-se desde o princípio a mesma forma, por vezes desconfortável ou mesmo inviável, de posicionamento na aquisição das imagens: decúbito dorsal com os braços elevados. OBJETIVOS: O objetivo da pesquisa foi o de avaliar se na aquisição da cintilografia de perfusão do miocárdio o posicionamento com os membros superiores abaixados(T) apresenta os mesmos resultados que os obtidos com os membros superiores elevados(C), tanto em termos de alterações perfusionais como em relação aos parâmetros funcionais. . MÉTODOS: Foram estudados 120 pacientes, 83 (69%) do sexo masculino, com idade 59,4 ± 11,4 anos e peso 72,8 ± 14 kg. Foi realizada primeiramente a aquisição C e na seqüência a aquisição T, utilizando protocolo de um dia de repouso-estresse (dose 370 MBq e 1110 MBq de sestamibi-99mTc), com estresse sincronizado ao eletrocardiograma (gated- SPECT). Três modelos distintos de equipamentos de dois detectores foram utilizados no estudo. Os estudos foram processados usando reconstrução iterativa (OSEM). Na interpretação foi utilizado o modelo de segmentação miocárdica de 17 segmentos, pontuados de 0 a 4 (normal a ausente) segundo o grau de captação. Baseada na análise de um observador dentre um grupo de sete, foi realizada a comparação da totalidade dos segmentos e também segmento a segmento das aquisições C e T nas etapas de estresse e de repouso. Foi comparada também a somatória das pontuações das etapas de estresse(SSS) e repouso(SRS). Os pacientes foram divididos segundo dois critérios: primeiramente, normais (SSS=0) e anormais (SSS>1) e posteriormente, em de baixo risco (SSS3) e de maior risco (SSS>3) A comparação dos parâmetros funcionais de fração de ejeção do ventrículo esquerdo (FEVE), volume diastólico final (VDF), volume sistólico final(VSF), somatória dos escores de motilidade (SMS) e somatória dos escores de espessamento (STS) foi baseada nos valores obtidos de modo automático utilizando o programa computacional Quantitative Gated SPECT. RESULTADOS: No modo C, 23,3% dos pts referiram algum grau de dor no membro superior ou no ombro e no modo T 5 %. Houve diferença significativa (p<0,05) na comparação dos 2040 segmentos miocárdicos entre C e T, ao estresse e ao repouso. Nos 63 pts normais não houve diferença significativa dos escores entre C e T ao estresse e ao repouso. O mesmo foi observado nos 80 pts de baixo risco. Nos 57 pts anormais houve boa correlação entre os valores de SSS (Rho=0,93, p=0,0001) e SRS (Rho=0,93, p=0,0001), mas com valores não equivalentes (p<0,05), sendo a média dos valores de SSS (9,28±8,10) e SRS (7,89±7,34) da aquisição T inferiores à média dos valores de SSS (10,07±7,71) e SRS (8,46±7,35) encontrada na aquisição C. Nos 40 pts de risco, houve boa correlação dos valores de SSS(Rho=0,95, p=0,0001) e SRS(Rho=0,96 p=0,0001), porém a média dos valores de SSS (12,53±7,54) e SRS (10,60±7,08) da aquisição T foi significantemente (p<0,05) inferior à média dos valores de SSS (13,43±6,81) e SRS(11,33±6,97) encontrados na aquisição C. Os parâmetros funcionais apresentaram boa correlação entre C e T, exceto o VDF(p=0,0001). CONCLUSÕES: Os modos C e T apresentam boa correlação dos parâmetros funcionais, exceto o VDF. Embora a aquisição T tenha sido um pouco mais confortável e tenha demonstrado boa correlação nos achados perfusionais, em pts anormais e de maior risco há tendência à subestimação dos defeitos perfusionais. Considerando a importância da medida precisa da intensidade e extensão das alterações perfusionais em termos de avaliação prognostica e decisão terapêutica, a aquisição com membro superior abaixado deve ser evitada. Em situações onde a aquisição com membros superiores abaixados é a única alternativa, os resultados da cintilografia devem ser interpretados com cuidado, especialmente em pacientes anormais e de maior risco, onde as alterações podem estar subestimadas / Contrary to the advances in imaging technology for nuclear cardiology applications, we keep using the same often uncomfortable and sometimes impracticable patient position- supine with arms raised above the head (C). We tested another position modality: supine with arms down at the sides of the trunk (T). The purpose of this study was to verify if the functional and perfusion results of the acquisition T are equivalent to those of the acquisition mode C. We studied 120 patients (pts), 83 (69%) male, aged 59.4±11.4 years and weighting 72.8±14 kg. We performed a one-day protocol (rest gated/stress), using 99mTc-sestamibi (370 MBq and 1110 MBq). In both times (rest and stress), we first performed acquisition in C and in sequence the acquisition in T. The studies were performed in three types of dual detector SPECT systems. T mode was executed successfully in all pts. Images were processed by the iterative reconstruction method (OSEM). Each study was independently interpreted by one nuclear medicine specialist from a group of seven physicians using the 17-segment model. The segments were scored using a 5-point model ranging from 0 (normal uptake) to 4 (uptake absent). The total score of the left ventricle at stress is referred to as the summed stress score (SSS) and at rest as the summed rest score (SRS). The patients were categorized in subgroups by two criteria: normal (SSS=0) or abnormal (SSS1) and low risk (SSS3) or risk (SSS>3). The values of the functional parameters of left ventricular ejection fraction (LVEF), end diastolic volume (EDV), end systolic volume (ESV), stress motion score (SMS) and stress thickening score (STS) for both C and T were automatically obtained by the quantitative gated SPECT (QGS) program and results were compared. Shoulder and/or back pain occurred in 23.3% of C patients and in 5% of T patients. There was no agreement between the 2040 segmental scores of both rest and stress in C and T modes (p<0.05). No significant differences between C and T were found for SSS and SRS in the 63 normal individuals nor in the 80 low risk patients. Good correlation between C and T was found for SSS (Rho=0.95, p=0.0001) and SRS (Rho=0.96 p=0.0001) in the 57 abnormal pts, but the mean SSS (9.28±8.10) and SRS (7.89±7.34) values of T were significantly lower (p<0.05) than the mean for SSS (10.07±7,71) and SRS(8.46±7,35) of C mode. Similar patterns were observed in the 40 risk pts; good correlation was found between C and T modes for SSS (Rho=0.95, p=0.0001) and SRS (Rho=0.96 p=0.0001), but the mean SSS (12.53±7.54) and SRS (10.60±7.08) values of T were significantly lower (p<0.05) than SSS (13.43±6.81) and SRS (11.33±6.97) of C mode. Good correlation between C and T was found for all functional parameters, except for EDV (p=0.0001). Although T mode appears to be more comfortable and presented a good correlation between SSS and SRS values, in abnormal and risk pts, the extent and severity of defects can be underestimated. Considering the important therapeutic and prognostic implications of an accurate perfusion measurement, the cardiac SPECT acquisition with the arms in down position should be avoided. When arms-down acquisition is the only alternative, scintigraphy results must be carefully interpreted, especially in abnormal scans whereas the amount of perfusion abnormalities can be underestimated.

Pacientes com diagnósticos oncológicos diversos sob terapia com agentes nefrotóxicos, foram avaliados através de procedimentos radioisotópicos, em três momentos diferentes. Os achados radioisotópicos foram comparados com as avaliações laboratoriais rotineiras. Não mostraram alterações estatisticamente significativas os seguintes parâmetros: uréia, creatinina, sedimentos anormais e índice de Crockoft-Gault. Concluiu-se que a avaliação da função renal com os métodos rotineiramente utilizados na prática oncológica não foram estatisticamente significativas. Dentre os estudos utilizando radionuclídeos, o DTPA-99mTc e DMSA-99mTc, evidenciaram alterações, enquanto o EC-99mTc, não as detectou / Patients with different oncologic diagnoses under treatment with nephrotoxic drugs were evaluated by radioisotopic agents at three different moments. Radioisotopic data were compared with biochemical routine tests. Concerning laboratorial parameters like serum creatinine, urea and Cockroft Gault index, no statistically significant changes were observed. Possible to conclude that renal function evaluation with methods routinely used in oncological practice did not reveal any statistically significant change. Radioisotopic studies using 99mTc-DTPA and 99mTc-DMSA showed considerable alterations, however with 99mTc-EC no significant changes were evidenced

Interstitial brachytherapy using permanent seeds is a common modality for the treatment of early stage prostate cancer. It consists of inserting hundreds of radioactive seeds (size of a grain of rice) in the prostate by means of transperineal needles. In this procedure, dose delivery to healthy surrounding organs at risk (OAR) and dose homogeneity within the prostate are of prime concern. Placement errors should therefore be minimized to avoid unacceptable area underdosage or overdosage. At present, brachytherapy seeds can be loaded with three different radionuclides: iodine-125 (¹²⁵I: 28.37 keV; 59.40 days), palladium-103 (¹⁰³Pd: 20.74 keV; 16.991 days), and cesium-131 (¹³¹Cs: 30.45 keV; 9.689 days). Long or short term morbidity is the main drawback of ¹²⁵I and ¹³¹Cs due to their deeper penetration in the normal tissues. However, both provide a good homogeneity of the dose distribution within the prostate. By contrast, ¹⁰³Pd offers a short penetration depth that reduces the dose to OAR. Nevertheless, it could result in cold spot (underdosage) where a recurrence of the cancer could appear. A compromise had to be found between good implant uniformity and low dose to OAR. We propose therefore to study if the combination of two radionuclides inside the same seed could be a solution. Two mixtures were considered: ¹⁰³Pd_0.75-¹²⁵I_0.25 and ¹⁰³Pd_0.25-¹³¹Cs_0.75. The subscripts denote the fractions of internal activity of each radionuclide. The work is subdivided into three steps. First we adapt the AAPM TG-43U1 dosimetry formalism used by the physician to make multiple-radionuclides sources compatible with Treatment Planning Systems (TPS). Then the dose distributions around the bi-radionuclide seeds are determined. Second, the prescription doses for both sources are derived using the linear quadratic model for tumor cell surviving fraction. They were computed using mono-radionuclide implants as benchmarks. Finally, treatment plans and Dose-Volume Histograms parameters have been computed on real patients virtually implanted with bi-radionuclide seeds and the results were compared with the mono-radionuclide one. These parameters can then be used to evaluate the Normal Tissue Complication Probability (NTCP) of urethra, the most exposed organ at risk in prostate brachytherapy. First, dosimetry results show that, from a pure physical point of view (i.e. without tissue reponse), the dose distributions of both mixtures lies in between that for ¹⁰³Pd and ¹²⁵I/¹³¹Cs. The compromise between homogeneity and reduced dose at large distance can be reached. Second, the averaged prescription doses for the Pd-I mixture are 142⁺¹⁵_-16Gy and 142⁺⁶_-8Gy using ¹⁰³Pd and ¹²⁵I as benchmarks, respectively. The values for the Pd Cs mixture are 128⁺¹³_-13Gy and 115⁺⁶_-7Gy, using ¹⁰³Pd and ¹³¹Cs, respectively, as benchmarks. Finally, urethral NTCP results fall in the 19 to 23% range. However, they are affected by large uncertainties, making the comparison difficult. At present, no conclusion could be drawn about the efficiency of bi-radionuclide brachytherapy in comparison with mono-radionuclide using the available models. Permanent seed prostate brachytherapy suffers a lot from the lack of precision on radiobiological modelling parameters. A better knowledge of their values could significantly improve the predicting models and therefore lead to better treatment outcome.