Estudo da perfusão pulmonar em crianças hospitalizadas com bronquite viral aguda por meio da cintilografia pulmonar perfusional quantitativa com 99mTC-MMA

Introdução: O conhecimento da distribuição da perfusão pulmonar pela cintilografia na bronquiolite viral aguda, pode auxiliar no entendimento das alterações no equilíbrio da ventilação - perfusão, peculiares a essa doença do lactente jovem. Objetivo: Avaliar o padrão de distribuição da perfusão pulmonar em pacientes hospitalizados com bronquiolite viral aguda por meio de cintilografia pulmonar perfusional quantitativa com macroagregado de albumina com tecnécio (99mTc-MAA), estabelecendo associação com as avaliações clínica e radiológica, bem como determinando o seu padrão evolutivo até a condição de normalidade. Tipo de estudo: Dois estudos prospectivos com enfoque diagnóstico: um transversal, comparativo, e um longitudinal, evolutivo, controlado. Pacientes e métodos: A amostra da pesquisa foi constituída por pacientes hospitalizados no Hospital de Clínicas de Porto Alegre com diagnóstico de bronquiolite viral aguda, no período de abril de 1998 a setembro de 2000, baseada em critérios clínicos de inclusão: idade entre 01 e 24 meses, com quadro respiratório obstrutivo de vias aéreas inferiores (primeiro episódio de sibilância expiratória de início súbito, com sinais de coriza, tosse irritativa, hipertermia, taquipnéia, tiragem, batimentos de asa de nariz, esforço expiratório), com gravidade suficiente para determinar a hospitalização e cujos pais aceitaram participar do estudo. Todos os pacientes da pesquisa foram submetidos à avaliação clínica, radiológica e da perfusão pulmonar com o radiofármaco. A cintilografia foi realizada na condição de crise (primeiras 24 horas da admissão) e na convalescência (depois de 7 dias da alta hospitalar). A quantificação do fluxo sangüíneo pulmonar, representada em valores percentuais, foi realizada em três áreas de interesse, nas projeções anterior e posterior, de ambos os pulmões. As comparações foram feitas entre ambos os pulmões e entre as condições de crise e controle, considerando as áreas de interesse e os gradientes entre elas e entre as projeções anterior e posterior das mesmas. Para análise comparativa das médias foi utilizado o teste t de Student para amostras pareadas, considerando o nível de significância de 0,05. Resultados: Iniciaram o estudo transversal 38 pacientes e permaneceram no estudo longitudinal 19 pacientes; da amostra total, 22 eram do sexo masculino. A idade variou de 1 a 8 meses (média 2,8 meses). A distribuição do fluxo sangüíneo pulmonar regional foi maior na região superior do pulmão esquerdo (PE) em relação ao pulmão direito (PD), na crise (P < 0,001), e maior na região média do PD, no controle. Os gradientes de distribuição do fluxo sangüíneo pulmonar entre as regiões superior e média e superior e inferior foi maior no PE, na crise e no controle (P < 0,05). O gradiente de distribuição do fluxo sangüíneo pulmonar entre as regiões média e inferior foi maior no PD, na crise e no controle. O gradiente de distribuição do fluxo sangüíneo pulmonar no eixo ântero-posterior na região superior foi > 1,0 em ambos os pulmões, na crise, e apenas no PE, no controle; na região média, foi > 1,0 em ambos os pulmões, na crise e no controle; na região inferior, foi > 1,0 apenas no PD, na crise e no controle (P < 0,05). A distribuição do fluxo sangüíneo pulmonar, comparada entre crise e controle, não mostrou diferença em quaisquer das regiões ou dos gradientes avaliados. Não houve associação entre o padrão de distribuição do fluxo sangüíneo pulmonar regional na crise com a avaliação clínica ou com a avaliação radiológica dos pacientes. Conclusão: não se evidenciou uma distribuição do fluxo sangüíneo pulmonar com caraterística de expressar o padrão da relação ventilação-perfusão em lactentes jovens hospitalizados com bronquiolite viral aguda. Ocorreu apenas uma tendência de redirecionamento da distribuição do fluxo sangüíneo pulmonar para as regiões superiores.

Cintilografia miocárdica quantitativa com Tc-99m sestamibi e correção de atenuação : desenvolvimento de base de dados normal gênero-independente de estudos de perfusão miocárdica de estresse e validação multicêntrica em população de pacientes obesos

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Translocation of 99mTc labelled bacteria after intestinal ischemia and reperfusion

Ischemia and reperfusion of the small intestine disrupts gut barrier, causes bacterial translocation and activates inflammatory responses. An experimental study was planned to evaluate if 99mTc labelled Escherichia coli translocates to mesenteric lymph nodes, liver, spleen, lung and serum of rats submitted to mesenteric ischemia/reperfusion. Additionally, it was observed if the time of reperfusion influences the level of translocation. METHODS: Forty male Wistar rats underwent 45 minutes of gut ischemia by occlusion of the superior mesenteric artery. The translocation of labelled bacteria to different organs and portal serum was determined in rats reperfused for 30 minutes, 24 hours, sham(S) and controls(C), using radioactivity count and colony forming units/g (CFU). RESULTS: All the organs from rats observed for 24 hours after reperfusion had higher levels of radioactivity and positive cultures (CFU) than did the organs of rats reperfused for 30 minutes, C and S, except in the spleen (p<0,01). CONCLUSION: The results of this study indicated that intestinal ischemia/reperfusion led to bacterial translocation, mostly after 24 hours of reperfusion

Influence of Splenectomy on the Biodistribution of Technetium-99m Dimercaptosuccinic Acid (99mTc-DMSA) in Rats

This study aimed to evaluate if the splenectomy alters the biodistribution of 99mTc-DMSA and renal function in Wistar rats. The animals were separated in the groups: splenectomy (n = 6) and control (n = 6). After splenectomy (15 days), the administration of 0.1ml of 99mTc-DMSA IV (0.48 MBq) was carried out. Thirty minutes later, kidney, heart, lung, thyroid, stomach, bladder and femur and samples of blood were isolated. The organs were weighed, counted and the percentage of radioactivity -g (%ATI-g) determined. Serum urea and creatinine, hematocrit, leukocytes and platelets were measured. Statistics by t test (p<0.05) was done. There was a significant reduction in %ATI-g in kidney and blood (p<0.05) of splenectomized animals, a significant increase (p<0.05) of urea (88.8 ± 18.6 mg-dL) and creatinine (0.56 ± 0.08 mg-dL), compared to the controls (51.5±1.6, 0.37±0.02mg-dL, respectively), as well as increase in platelets and leucocytes, and hematocrit reduction. The analysis of the results indicates that in rats, splenectomy seems to alter the renal function and the uptake of 99mTc-DMSA

Influência da esplenectomia na biodistribuição do ácido dimercaptosuccínico-tecnécio-99m (99mTc-DMSA) em ratos Wistar

A esplenectomia é indicada em doenças hematológicas, hiperesplenismo grave, traumas e tem sido causa de importantes alterações metabólicas e imunológicas. O objetivo do presente trabalho é avaliar se a retirada do baço altera a biodistribuição do radiofármaco DMSA Tc99m em ratos Wistar e se há correlação com possíveis alterações da função renal. Foram usados dois grupos: esplenectomia (n=6) e controle (n=6) animais não operados. Após 15 dias, foi administrado 0,1 ml de DMSA-Tc99m via plexo orbital (0,66 MBq). Trinta minutos depois, foram retiradas amostras do rim, coração, pulmão, tireóide, estômago, bexiga, fêmur, sangue. Após pesadas as amostras, foi determinado o percentual de radioatividade/g (% ATI/g) em cada uma delas, com o Wizard Gama Counter Perkin-Elmer . Dosadas uréia e creatinina sérica, hematócrito, plaquetas e leucócitos. Estatística pelo teste t, com significância 0,05. Foi observada redução significante no %ATI/g no rim e sangue (p<0,05) dos animais esplenectomizados, aumento significante (p<0,05) da uréia (88,8±18,6mg/dL) e creatinina (0,56±0,08), comparado aos controles (51,5±1,6 e 0,37±0,02mg/dL, respectivamente) assim como leucocitose, aumento de plaquetas e redução de hematócrito. Em conclusão, a esplenectomia provocou comprometimento da função renal, repercutindo na alteração da captação de DMSA 99mTc pelo rim de ratos. Uma parceria entre a Unidade de Medicina Nuclear da Liga Norteriograndense Contra o Câncer e o Núcleo de Cirurgia Experimental da Universidade Federal do Rio Grande doNorte tornou possível a realização deste trabalho, que contou com a participação de profissionais de diferentes áreas como: Biologia, Biomedicina, Medicina Nuclear, Cirurgia Geral, Bioquímica e Estatística, atestando dessa forma o caráter multidisciplinar do trabalho

Tc-99m-sestamibi scintigraphy used to evaluate tumor response to neoadjuvant chemotherapy in locally advanced breast cancer: A quantitative analysis

To evaluate the tumor response to neoadjuvant chemotherapy, Tc-99m-sestamibi breast scintigraphy was proposed as a quantitative method Fifty-five patients with ductal carcinoma were studied They underwent breast scintigraphy before and after neoadjuvant chemotherapy, along with clinical assessment and surgical specimen analysis The regions of interest on the lesion and contralateral breast were identified, and the pixel counts were used to evaluate lesion uptake in relation to background radiation The ratio of these counts before to after neoadjuvant chemotherapy was assessed The decrease in uptake rate due to chemotherapy characterized the scintigraphy tumor response The Kruskal-Wallis test was used to compare the mean scintigraphic tumor response and histological type Dunn's multiple comparison test was used to detect differences between histological types The Mann-Whitney test was used to compare means between quantitative and qualitative variables scintigraphic tumor response vs clinical response and uptake before chemotherapy vs scintigraphic tumor response The Spearman's test was used to correlate the quantitative variables of clinical reduction in tumor size and scintigraphic tumor response All of the variables compared presented significant differences The change in Tc-99m-sestamibi uptake noted on breast scintigraphy, before to after neoadjuvant chemotherapy, may be used as an effective method for evaluating the response to neoadjuvant chemotherapy, since this quantification reflects the biological behavior of the tumor towards the chemotherapy regimen Furthermore, additional analysis on the uptake rate before chemotherapy may accurately predict treatment response

Accuracy of Tc-99m-sestamibi scintimammography for breast cancer diagnosis

Scintimammography using Tc-99m-sestamibi is a noninvasive and painless diagnostic imaging method that is used to detect breast cancer when mammography is inconclusive Because of the advantages of labeling v '7,ith Tc-99m-sestamibi and its high efficiency in detecting carcinomas, it is the most widespread agent for this purpose Its accumulation in the tumor has multifactorial causes and does not depend on the presence of architectural distortion or local or diffuse density variation in the breast The objective of tfiis study was to evaluate the accuracy of scintimammography 1 for detecting breast cancer One hundred and fifty-seven patients presenting 158 palpable and non-palpable breast nodules were evaluated Three patients were male and 154 were female, aged between 14 and 81 years All patients underwent scintimammography, and the nodule was subjected i to cytological or histological study, i e, the gold standard for diagnosing cancer One hundred and eleven malignant and 47 benign nodules were detected, with predominance of ductal carcinomas (n=94) and fibroadenoma/fibrocysiic condition (n=11/n=11), respectively The mean size was 3 11 cm (7-10 cm) among the malignant nodules and 2 07 cm among the benign nodules (0 5-10 cm) The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 89, 89, 95, 78 and 89%, respectively Analysis on the histological types showed that the technique was more effective on tumors that were more aggressive, such as ductal carcinoma In this study, Tc-99m-sestamibi scintim immography was shown to be an important tool for diagnosing breast cancer when mammography was inconclusive

Evaluation of mammographic density and Tc-99m-sestamibi scintimammographic uptake in postmenopausal women on hormone replacement therapy

Objective: To evaluate changes in mammographic density and Tc-99m-sestamibi scintimammographic uptake in postmenopausal women on hormone replacement therapy (HRT).Methods: Seventy-five postmenopausal women were prospectively studied and allocated into three groups: 50 women were randomized to either Group 1 (G1, n = 25), which received 2 mg of 17 beta-oestradiol continuously combined with 1 mg of norethisterone acetate (E-2/NETA, Kliogest (R), Medley) or Group 2 (G2), which received 2.5 mg/day of tibolone (Livial (R), Organon). The remaining 25 women, who were asymptomatic and had no desire to undergo HRT, constituted the control group (G3). Each patient was submitted to both mammography and scintimammography at baseline and after six months. Mammographic density was evaluated by using the BI-RADS classification system. The classification system of Barros et al. was used in the interpretation of scintimammography. For statistical analysis, the Chi-square test, ANOVA and Pearson's correlation were used.Results: At six months, increased mammographic density was observed in 48% of G1, 12% of G2 and 16% of G3 patients (p < 0.001). The increase in sestamibi uptake was 56% in G1, 28% in G2 and 24% in G3 (p < 0.001). Increases in both density and uptake were significantly higher in the group on E-2/NETA than among tibolone users and the controls.Conclusion: In postmenopausal women, HRT with E-2/NETA was associated with increased mammographic density and increased Tc-99m-sestamibi scintimammographic uptakes, suggesting greater mithochondrial activity in the cells of the mammary duct. This was not observed in users of 2.5 mg of tibolone, demonstrating that the effects on the breast were reduced. The same was observed in the control group. (c) 2005 Elsevier B.V.. All rights reserved.

The influence of cardiopulmonary bypass operation on the biodistribution of 99mTc-HMPAO-labelled granulocytes – Evaluation in pigs by planar scintigraphy and section-analyses

Aim of the study was to evaluate the influence of an extra corporal perfusion (cardiopulmonary bypass operation - cpb) on activation and biodistribution of Tc-99m labelled granulocytes in pigs with and without inhibition of the granulocytes by a leukocyte inhibition module (LIM). The cpb is often related to an activation of granulocytes resulting in an inflammatory answer. The biological mechanisms are unsolved yet. First trials of our group showed that LIM may inhibit the activation of neutrophils and therefore antagonize a cpb-caused impairment of cardiac function. This study is the continuation of these experiments with a higher number of animals and the focus on scintigraphic imaging. Animals, material, methods: 39 German landrace pigs were subdivided into three groups: group A (control) median sternotomy without cpb, group B with cpb, group C with LIM in addition to cpb. After labelling with Tc-99m-HMPAO autologues granulocytes were reinjected. Subsequently to cpb, the animals underwent scintigraphic imaging. Quantification was performed with ROI evaluation and with tissue samples (section analysis) examined in a well counter. Results:A high uptake of Tc-99m-HMPAO was found in the liver. The count rates in brain, heart, lung, spleen and kidneys were far below. The amount of Tc-99m-activity in the organ related to the half life corrected administered activity [%] was for the tissue samples (group A/B/C): brain 0.01/0.02/0.03; lung 12.1/8.3/11.5; heart 0.35/0.54/0.42; kidney 1.24/0.87/1.02; spleen 4.0/4.0/4.5, liver 16.8/20.9/19.6. The count rates determined by ROI-evaluation of the scintigraphic images related to the total count rate in the image [%] were (group A/B/C): brain 1.1/0.9/1.0; lung 15.6/10.4/12.2; heart 4.0/3.5/3.4; kidney 4.0/2.9/3.2; spleen 7.6/7.7/9.5, liver 23.1/36.7/31.4. A significant difference in the tracer uptake between the groups could neither be detected by scintigraphic imaging nor evaluation of tissue samples. Conclusion: Scintigraphic imaging as well as section analysis showed a comparable biodistribution of the tracer. Therefore, the initial results of our group were not confirmed with a considerably higher number of animals. Neither cpb nor the use of the LIM influenced distribution of Tc-99m-labelled granulocytes in pigs significantly.

Efeito do módulo de inativação leucocitária (LIM) na distribuição de 99mTc-granulócitos em porcos submetidos à circulação extracorpórea e à isquemia-reperfusão de coração e pulmões

Pós-graduação em Bases Gerais da Cirurgia - FMB

Neovascularization after ischemic injury: evaluation with 99mTc-HYNIC-RGD

Purpose: Angiogenesis involves many mediators including integrins, and the tripeptide RGD is a target amino acid recognition sequence for many of them. Hindlimb ischemia is a simple and convenient animal model however standardization of the injection procedures in the devascularized and control limb is lacking, thus rendering difficult the interpretation of results. The aim of this investigations was to evaluate neovascularization in a hindlimb murine model by means of 99mTc-HYNIC-ß-Ala-RGD. Methods: 99mTc-HYNIC-RGD analog was prepared using coligands. Ischemia was induced in Wistar rats by double- ligation of the common femoral artery. Radiolabeled RGD was injected after 2h, as well as 1, 3, 5, 7, 10 and 14 days. Uptake was evaluated by planar imaging and biodistribution studies. Results: The highest ratio between ischemia and control was achieved at the 7th day (2.62 ± 0.95), with substantial decrease by the 14th day. For pertechnetate the 7th day ratio was 0.87 ± 0.23. Scintigraphic image confirmed different uptakes. Conclusion: 99mTc-HYNIC-RGD analog concentrated in ischemic tissue by the time of widespread angiogenesis and pertechnetate confirmed reduction in blood flow. In this sense, the protocol can be recommended for ischemic models.

Biopsia selectiva del ganglio centinela con 99mTc-nanocoloides en el cáncer de mama : validación de la técnica, implantación y análisis del impacto sobre el pronóstico de la enfermedad

Programa de doctorado: Avances en Medicina Interna.

Synthese und Evaluierung von 68Ga-Schiff'schen Basen zur Diagnostik der koronaren Herzerkrankung

ZusammenfassungrnDie häufigsten Todesfälle weltweit sind auf Herzerkrankungen zurückzuführen. Bei der koronaren Herzkrankheit (KHK) sammeln sich über Jahre arteriosklerotische Ablagerungen in den Herzkranzgefäßen an und führen so zu einer verminderten Durchblutung und Versorgung des Herzmuskelgewebes mit Sauerstoff und Nährstoffen. Zur nuklearmedizinischen Bildgebung finden am häufigsten das SPECT-Nuklid 201Tl sowie die beiden 99mTc-Radiopharmaka Sestamibi und Tetrofosmin Anwendung. Die PET-Technik ist der SPECT-Technik in Bezug auf absolute Quantifizierung sowie Auflösung überlegen. Ziel der vorliegenden Arbeit war es, ein mögliches PET-Radiopharmakon zur Diagnostik der KHK zu entwickeln. Um eine dem 99mTc-Nuklid vergleichbare Verfügbarkeit im klinischen Alltag zu erreichen, sollte als Basis des neuen Radiopharmakons das mittels Radionuklid-Generator verfügbare 68Ga dienen. Schiff’sche Basen-Verbindungen zeigten nach Komplexierung mit 67/68Ga eine deutliche Aufnahme in die Herzmuskelzellen. Auf dieser Grundlage wurden verschiedene Schiff’sche Basen-Strukturen synthetisiert. Diese unterscheiden sich einerseits durch das Substitutionsmuster der verwendeten Aldehyde und andererseits durch das verwendete Rückgrat. Alle synthetisierten Chelatoren wurden erfolgreich mit 68Ga radioaktiv markiert und konnten anschließend aufgereinigt werden. Die Evaluierung dieser Substanzen in vitro zeigte, dass sie in unterschiedlichen Medien stabil ist. Die Lipophilie der 68Ga-Verbindungen (log D) lag zwischen 0,87±0,24 und 2,72±0,14. Die Ladung der Verbindungen wurde mittels Papierelektrophorese bei pH= 7 als kationisch bestimmt. Zusätzlich fanden in vitro-Untersuchungen zur Bestimmung der Aufnahme der Komplexe in HL-1 Herzzellen statt. Um den Einfluss des Zellmembranpotentials bzw. des Mitochondrienmembranpotentials zu untersuchen, wurde ein Teil der Zellen dafür mit Valinomycin (Ionophor, zerstört das Potential) behandelt. Mittels ex vivo-Biodistributionen wurde die Organverteilung von zwei Schiff’schen Basen (68Ga-BADED-2 und 68Ga-BAPDMEN-2) mit dem routinemäßig in der Klinik eingesetzten Derivat 99mTc-Sestamibi sowie dem 18F-Flurpiridaz in Ratten verglichen. Alle Verbindungen zeigten dabei eine deutliche Herzaufnahme von mehr als 2 % der injizierten Dosis pro Gramm Gewebe. Durch in vivo-PET-Aufnahmen wurden die Zeit-Aktivitätskurven der 68Ga-Verbindungen sowie zum Vergleich des 18F-Flurpiridaz bestimmt. Die Aufnahmen lagen im Bereich von 0,63±0,15 für 68Ga-BAPEN-3 bis 2,72±0,86 für 68Ga-BADED-8.In dem zweiten Teil der Arbeit wurden die Vorteile des hochaffinen Herztracers Flurpiridaz mit dem lipophilen, positiv-geladenen Ga-Schiff’sche Base-Chelator kombiniert. Hierzu wurde zunächst das Insektizid Flurpiridaz synthetisiert und mit dem BAPEN-Rückgrat gekoppelt. Die entstandene Verbindung wurde erstmals mit 68Ga radioaktiv markiert und muss in weiterführenden Arbeiten evaluiert werden.

Un target a basso costo per la produzione diretta di 99mTc mediante ciclotrone

In Medicina Nucleare è possibile ottenere immagini funzionali grazie all’iniezione nel paziente di un radiofarmaco. Quello più utilizzato nelle procedure diagnostiche di Medicina Nucleare è il 99mTc, un gamma emettitore con tempo di dimezzamento di circa sei ore. Attualmente, questo nuclide è prodotto attraverso generatori di 99Mo-99mTc, sfruttando il decadimento β- del 99Mo. Da diversi anni, però, si cerca in tutto il mondo una soluzione alternativa alla produzione di 99mTc, poiché il 99Mo si ottiene in reattori nucleari a partire dalla reazione di fissione del 235U, ma tali reattori sono stati quasi tutti costruiti più di cinquanta anni fa e necessitano continuamente di spegnimenti prolungati e riparazioni. L’alternativa più accreditata è quella relativa alla produzione diretta di 99mTc in ciclotrone attraverso l’irraggiamento di 100Mo con protoni. Il problema principale risiede nella scelta della forma chimica che contenga il 100Mo e del tipo di target da irraggiare. Quest’ultimo deve resistere ad alte correnti e a lunghi tempi di irraggiamento per ottenere quantità di 99mTc sufficienti a soddisfare almeno il fabbisogno del centro ospedaliero in cui è prodotto. Questo lavoro di tesi, svolto presso il Servizio di Fisica Sanitaria del Policlinico S.Orsola-Malpighi, è basato sulla realizzazione di un target a basso costo di triossido Molibdeno arricchito per la produzione diretta di 99mTc. Si sono inoltre valutate le impurezze e l’attività del nuclide di nostro interesse a seguito di irraggiamenti nel ciclotrone PETtrace.