99mTc-HYNIC/Cy7-Fab(Bevacizumab): su empleo como agente de imagen en mieloma múltiple / 99mTc-HYNIC/Cy7-Fab(Bevacizumab): its use as an imaging agent in Multiple Myeloma / 99mTc-HYNIC/Cy7-Fab (Bevacizumab): seu uso como agente de imagem em mieloma múltiplo

Introducción: el mieloma múltiple es un trastorno hematológico maligno y el segundo cáncer de la sangre más frecuente. El proceso de la angiogénesis tumoral es fundamental para el crecimiento y metástasis de muchos tipos de tumores, incluido en mieloma múltiple. Se sabe que la sobreexpresión del factor de crecimiento endothelial vascular se encuentra asociado a un mal pronóstico en esta patología, representando un blanco clave para la terapia anti-angiogénica en mieloma múltiple. El anticuerpo monoclonal Bevacizumab es capaz de unirse con gran afinidad al factor de crecimiento endothelial vascular bloqueando su acción. Objetivo: evaluar el Fab(Bevacizumab) marcado con 99mTc o Cy7 como potenciales agentes de imagen moleculares de la expresión de factor de crecimiento endothelial vascular en mieloma múltiple. Material y métodos: la expresión de factor de crecimiento endothelial vascular fue analizada mediante citometría de flujo en la línea celular huaman de mieloma múltiple, la MM1S. Fab(Bevacizumab) fue producido mediante digestión de Bevacizumab con papaína, conjugado a NHS-HYNIC-Tfa y radiomarcado con 99mTc. Se realizaron estudios de biodistribución y de tomografía computarizada por emisión del fotón simple. A su vez, Fab(Bevacizumab) fue marcado con Cy7 para obtener imágenes de fluorescencia in vivo hasta 96 horas. Resultados: el análisis por citometría de flujo en la línea celular MM1S reveló que la expresión de factor de crecimiento endothelial vascular es predominantemente intracelular. Los estudios de biodistribución y SPECT/CT del complejo 99mTc-HYNIC-Fab(Bevacizumab) mostraron una rápida eliminación sanguínea y una significativa captación a nivel renal y tumoral. Las imágenes por fluorescencia empleando Cy7-Fab(Bevacizumab) permitieron la visualización tumoral hasta 96 h p.i. Conclusiones: logramos visualizar la expresión de factor de crecimiento endothelial vascular in vivo en mieloma múltiple mediante el empleo del fragmento Fab del anticuerpo anti-VEGF (Bevacizumab) marcado con 99mTc y Cy7. Estos nuevos agentes de imagen molecular podrían ser empleados potencialmente en el ámbito clínico para la estadificación y el seguimiento de pacientes con mieloma múltiple, mediante la visualización radioactiva in vivo de la expresión de factor de crecimiento endothelial vascular en todo el cuerpo. La imagen óptica de estos trazadores mejoraría el muestreo tumoral y podría guiar la extirpación quirúrgica.

Introduction: Multiple myeloma is a hematologic malignancy and the second most common blood cancer. The process of tumor angiogenesis is central to the growth and metastasis of many types of tumors, including multiple myeloma. Overexpression of vascular endothelial growth factor is known to be associated with poor prognosis in this pathology, representing a key target for anti-angiogenic therapy in multiple myeloma. The monoclonal antibody Bevacizumab is able to bind with high affinity to vascular endothelial growth factor blocking its action. Objective: to evaluate 99mTc- or Cy7-labeled Fab(Bevacizumab) as potential molecular imaging agents of vascular endothelial growth factor expression in multiple myeloma. Methods: Vascular endothelial growth factor expression was analyzed by flow cytometry in the multiple myeloma huaman cell line, MM1S. Fab(Bevacizumab) was produced by digestion of Bevacizumab with papain, conjugated to NHS-HYNIC-Tfa and radiolabeled with 99mTc. Biodistribution and single photon emission computed tomography studies were performed. In turn, Fab(Bevacizumab) was labeled with Cy7 to obtain in vivo fluorescence images up to 96 hours. Results: Flow cytometry analysis in the MM1S cell line revealed that vascular endothelial growth factor expression is predominantly intracellular. Biodistribution and SPECT/CT studies of the 99mTc-HYNIC-Fab(Bevacizumab) complex showed rapid blood clearance and significant renal and tumor uptake. Fluorescence imaging using Cy7-Fab(Bevacizumab) allowed tumor visualization up to 96 h p.i. Conclusions: we were able to visualize vascular endothelial growth factor expression in vivo in multiple myeloma using the Fab fragment of the anti-VEGF antibody (Bevacizumab) labeled with 99mTc and Cy7. These new molecular imaging agents could potentially be employed in the clinical setting for staging and monitoring of patients with multiple myeloma by in vivo radioactive visualization of vascular endothelial growth factor expression throughout the body. Optical imaging of these tracers would improve tumor sampling and could guide surgical excision.

Introdução: O mieloma múltiplo é uma malignidade hematológica e o segundo câncer de sangue mais comum. O processo de angiogênese tumoral é fundamental para o crescimento e a metástase de muitos tipos de tumores, incluindo o mieloma múltiplo. Sabe-se que a superexpressão do fator de crescimento endotelial vascular está associada a um prognóstico ruim no mieloma múltiplo, representando um alvo importante para a terapia antiangiogênica no mieloma múltiplo. O anticorpo monoclonal Bevacizumab é capaz de se ligar com alta afinidade ao fator de crescimento endotelial vascular e bloquear sua ação. Objetivo: avaliar o Fab(Bevacizumab) marcado com 99mTc ou Cy7 como possíveis agentes de imagem molecular da expressão do fator de crescimento endotelial vascular no mieloma múltiplo. Métodos: A expressão do fator de crescimento endotelial vascular foi analisada por citometria de fluxo na linha celular de mieloma múltiplo MM1S. O Fab(Bevacizumab) foi produzido pela digestão do Bevacizumab com papaína, conjugado com NHS-HYNIC-Tfa e radiomarcado com 99mTc. Foram realizados estudos de biodistribuição e tomografia computadorizada por emissão de fóton único. Por sua vez, o Fab(Bevacizumab) foi marcado com Cy7 para geração de imagens de fluorescência in vivo por até 96 horas. Resultados: A análise de citometria de fluxo na linha celular MM1S revelou que a expressão do fator de crescimento endotelial vascular é predominantemente intracelular. Os estudos de biodistribuição e SPECT/CT do complexo 99mTc-HYNIC-Fab(Bevacizumab) mostraram uma rápida depuração sanguínea e uma captação renal e tumoral significativa. A imagem de fluorescência usando Cy7-Fab(Bevacizumab) permitiu a visualização do tumor até 96 horas p.i. Conclusões: Conseguimos visualizar a expressão do fator de crescimento endotelial vascular in vivo no mieloma múltiplo usando o fragmento Fab do anticorpo anti-VEGF (Bevacizumab) marcado com 99mTc e Cy7. Esses novos agentes de imagem molecular poderiam ser usados no cenário clínico para o estadiamento e o monitoramento de pacientes com mieloma múltiplo, visualizando radioativamente a expressão do fator de crescimento endotelial vascular in vivo em todo o corpo. A geração de imagens ópticas desses traçadores melhoraria a amostragem do tumor e poderia orientar a excisão cirúrgica.

Utilização de radiofármacos marcados com tecnécio 99m como potenciais marcadores na obtenção de imagens de perfusão miocárdica / Using technetium-99m-marked radiopharmaceuticals as potential markers in obtaining myocardial perfusion images

A Organização Mundial de Saúde (OMS) aponta as doenças cardiovasculares como a principal causa de morte no mundo, caracterizando um grave problema na saúde pública. Os três tipos de doenças que mais acarretam em óbito são: acidente vascular cerebral, seguido de infarto agudo do miocárdio e outras doenças isquêmicas do coração.Apesar dos avanços terapêuticos das últimas décadas, o infarto ainda apresenta altas taxas de mortalidade. Para as pessoas com doenças cardiovasculares ou com alto risco cardiovascular é fundamental o diagnóstico precoce da doença. A cintilografia de perfusão miocárdica é um método de investigação diagnóstica e prognóstico não invasivo de várias doenças cardiovasculares. Esse exame consiste na administração de um radiofármaco para obtenção de imagens de perfusão cardíaca. Dois traçadores marcados com Tecnécio-99m são amplamente utilizados na clínica, porém, esses dois radiofármacos não atendem aos requisitos de um agente de perfusão ideal, por sofrerem significativa excreção biliar, produzindo artefatos na imagem, o que pode inteferir um diagnóstico preciso, já que a qualidade é comprometida, e prolongando o tempo de obtenção da imagem após a administração do radiotraçador. Para superar essa lacuna, pesquisadores vêm estudando novos complexos catiônicos marcados com o Tecnécio. O objetivo desse artigo é fazer uma revisão, abordando a literatura sobre os radiofármacos que estão sendo estudados, suas vantagens e desvantagens sobre os traçadores já utilizados, e sobre sua potencial utilização na obtenção de imagem de perfusão cardíaca.

The World Health Organization (WHO) acknowledges cardiovascular diseases as the leading cause of death in the world, being regarded as a serious public health issue. The three types of diseases with the greatest mortality are: stroke, followed by acute myocardial infarction (AMI) and other ischemic heart diseases. Despite the therapeutic advances of the last decades, AMI still presents high mortality rates. Early diagnosis is essential for people with cardiovascular diseases or with a high cardiovascular risk. Myocardial perfusion scintigraphy is a method of diagnostic investigation and noninvasive prognosis of various cardiovascular diseases. This examination consists in the administration of a radiopharmaceutical drug to obtain images of cardiac perfusion. Two tracers labeled with Technetium-99m are widely used, however, these two radiopharmaceuticals do not meet the requirements of an ideal perfusion agent, because they have a high liver absorption, producing artifacts in the image, which can disrupt a precise diagnosis, since the quality is compromised, and prolonging the imaging time after administration of the radioisotope. To overcome this gap, researchers have been studying new cationic complexes marked with technetium. The objective of this article is to review the literature on the radiopharmaceuticals being studied, their advantages and disadvantages on the tracers already used, and their potential use in obtaining a cardiac perfusion image.

Evaluación biológica de 99mTc-voriconazol como potencial agente de diagnóstico de infecciones fúngicas por centellografía gamma / Biological evaluation of voriconazole with 99mTc for the diagnosis of fungal infections

El avance del HIV ha favorecido el aumento de infecciones fúngicas como candidiasis y aspergilosis invasivas. Varias clases de antifúngicos son utilizados para el tratamiento de las mismas y éstos pueden ser radiomarcados con un agente emisor gamma que permita la detección mediante centellografia de focos de infección. El Voriconazol es un triazol adecuado para la marcación mediante la formación de un complejo unido al precursor [99mTc(H2O)3(CO)3]+. El objetivo fue marcar y determinar las características fisicoquímicas y biológicas del voriconazol con 99mTc para la detección temprana de infecciones. La pureza radioquímica se determinó por HPLC y permitió establecer que el complejo permanece estable durante al menos 120 min. Los estudios in vivo en modelos de inflamación estéril, infección con C. Albicans y A. Niger mostraron diferenciación de los procesos tanto en biodistribución como en imágenes centellográficas.

The spread of HIV has led to an increase of fungal infections such as candidiasis and invasive aspergillosis. Several types of antifungals are used to treat them and some of them can be radiolabeled with a gamma emitting agent to allow detection by scintigraphy of foci of infection. Voriconazole is a triazole agent, suitable for the synthesis of a complex linked with the precursor [99mTc(H2O)3(CO)3]+. The aim of his work was to label and determine the physicochemical and biological characteristics of voriconazole with 99mTc for the early detection of fungal infections. Radiochemical purity was determined by HPLC and the complex remained stable during at least 120 min. In vivo studies in rats bearing either sterile inflammation, infection with C. Albicans or A. Niger showed differentiation of the processes not only in biosdistribution but also in scintigraphic images.

Marcación de un derivado de glucosa con 99mTc mediante la formación de un complejo Tc(V)-nitruro: estudios preliminares / Labelling of a glucose derivative with 99mTc through the formation of a Tc(V)-nitride symmetrical complex: preliminary studies

La preparación de derivados de glucosa marcados con 99mTc reviste gran interés para la evaluación del consumo de glucosa in vivo en oncología y cardiología nuclear. Este trabajo presenta la marcación de un análogo de glucosa (GLU-DTC) mediante la formación de un complejo Tc(V)-nitruro simétrico. Para ello se incorporó a la biomolécula un grupo ditiocarbamato capaz de coordinar al metal. La marcación fue realizada mediante sustitución de ligandos, obteniéndose una única especie con pureza radioquímica superior al 90 por cientp, la que se mantuvo durante al menos 4 hs. La caracterización fisicoquímica y biológica muestra que el complejo 99mTc(V)-nitruro(GLU-DTC)2 es un compuesto estable y altamente hidrofílico, aunque su unión a proteínas plasmáticas es mayor a la esperada, hecho que justificaría la alta actividad retenida en sangre y en hígado durante la evaluación biológica en ratones CD1 normales. Estos resultados indican que la marcación con 99mTc de este derivado de glucosa produce una alteración significativa de su comportamiento biológico.

The preparation of 99mTc-labeled glucose derivatives is of great interest to evaluate the in vivo glucose uptake in nuclear oncology and cardiology. This paper presents the labelling of a glucose analogue (GLU-DTC) through the formation of a Tc(V)-nitride symmetrical complex. For this purpose, a dithiocarbamate group was incorporated to the biomolecule, in order to coordinate the metal. The labelling reaction was carried out by substitution yielding a single complex with radiochemical purity above 90 percent. This complex was stable for at least 4 hours. The physicochemical and biological characterization shows that the 99mTc(V)-nitride(GLU-DTC)2 complex is a stable and highly hydrophilic compound, although its plasma protein binding is greater than expected, a fact which justifies the high activity retained in blood and liver during the biological evaluation in normal CD1 mice. These results indicate that 99mTc labelling of this glucose derivate alters significantly its biological behaviour.

Marcado con 99m de liposomas convencionales y su evaluación biológica / 99mTc-labeling and biological evaluation of conventional liposomes

Introducción. Los liposomas son sistemas supramoleculares autoensamblables preparados ad hoc, compuestos de fosfolípidos y colesterol, diseñados para transporte de fármacos o radionucleidos. El 99mTc es el radionucleido más empleado por sus propiedades físicas apropiadas para la adquisición de imágenes y estudios en pacientes en el área de medicina nuclear (emisor gamma puro con E = 140 KeV , t1/2 = 6 horas). Objetivo. Evaluar la potencialidad de liposomas convencionales marcados con 99mTc como agente de diagnóstico de procesos tumorales. Método. La composición estudiada es: fosfatidilcolina, dioleilfosfatidiletanolamina y colesterol (1.1:0.4:1 relación molar). Se utilizó como agente reductor SnF2, en diferentes cantidades para optimizar el marcado. La pureza radioquímica y eficiencia de marcado se evaluaron con sistemas cromatográficos ITLC-SG FM NaCl 0,9 por ciento, ITLC-SG FM Piridina:ácido acético:agua (3:5:1.5 v/v). Se adquirieron imágenes a 1 h post inyección de los liposomas en ratones sanos y portadores de tumor mamario espontáneo. Resultados. El liposoma marcado mostró estabilidad durante 24 h, siendo la cantidad óptima de reductor 138 ug. La mejor captación en tumor fue a 1 h post administración del radiofármaco en los estudios centellográficos. Conclusiones. El método optimizado permite obtener liposomas marcados con 99mTc en forma sencilla, eficiente y estable. Estos radiofármacos mostraron un comportamiento fiscoquímico y biológico adecuado como agentes de diagnóstico tumoral requiriéndose estudios posteriores para su confirmación.

Background. Liposomes are self-assembled supramolecular systems, composed by phospholipids and cholesterol, designed for the transportation of drugs or radionuclides. Physical properties of 99mTc (pure gamma emitter with E = 140 KeV, t1/2= 6 hours) makes it useful for scintigraphic imaging. Purpose. The goal of this study was to evaluate 99mTc labeled conventional liposomes as potential diagnostic agents for malignant lesions. Methods. The studied liposome composition was hosphatidylcholine: dioleilphosphatidylcholine: cholesterol (1.1:0.4:1molar rate). In order to optimize the labeling, SnF2 was used as reducing agent. Radiochemical purity and labeling efficiency were evaluated using ascending thin layer chromatography. Scintigraphy images were obtained at 1 hour post-injection of labeled liposomes to healthy mice and with spontaneous breast tumors. Results. Labeled liposomes showed stability during 24 hours, being 138 ug the optimal amount of reducing agent for the technique used. Conclusions. The described method allows the production of 99mTc labeled liposomes in a simple, efficient and stable way. The radiopharmaceutical showed a physicochemical and biological behavior that allows its potential use as a tumor imaging agent, although further studies are required to confirm this issue.

Desarrollo de un péptido cíclico marcado con 99mTc dirigido contra el receptor de la vitronectina / Development of a 99mTc-labeled cyclic peptide with affinity for the vitronectine receptor

El objetivo del presente trabajo fue desarrollar un péptido híbrido, que presente una secuencia capaz de quelatar al 99mTc y otra con afinidad por el receptor de la vitronectina, que permita la detección in vivo de tumores malignos. El marcaje del péptido PICIC3 con 99mTc se realizó de forma directa. Se estudió la estabilidad del complejo en exceso de L-cisteína y en plasma, la unión a proteínas plasmáticas, el coeficiente de partición en el sistema NaCl 0.9 por ciento:n-octanol, la carga del complejo mediante electroforesis y la afinidad por el receptor de la vitronectina se valoró a partir de un ensayo de saturación con membranas de células B16-F10. Se determinó la biodistribución en ratones C57BL/6 con injertos de melanoma B16-F10. Conclusiones: El péptido desarrollado mostró una afinidad satisfactoria por el receptor de la vitronectina y que permitió la detección in vivo de los melanomas múridos del tipo B16-F10 en los ratones injertados.

The aim of the present work was to develop a hybrid peptide, with a sequence for the chelation of 99mTc and other with affinity for the vitronectine receptor, to allow in vivo detection of malignant tumors. 99mTc-labeling of peptide PICIC3 was directly performed. The stability in presence of L-cysteine excess and plasma of the complex, its binding to plasma proteins, the partition coefficient in NaCl 0.9 percent:n-octanol, the charge of the chelate by electrophoresis and the peptide affinity for the vitronectine receptor by a saturation assay using membranes of B16-F10 cells, were studied. Biodistribution in C57BL/6 mice injerted with melanoma B16-F10 was assessed. Conclusions: Developed peptide showed a satisfactory affinity for the vitronectine receptor and allowed in vivo detection of murine melanomas in mice with allografts.

Deposição pulmonar de tobramicina inalatória antes e após fisioterapia respiratória e uso de salbutamol inalatório em pacientes com fibrose cística colonizados por Pseudomonas aeruginosa / Pulmonary deposition of inhaled tobramycin prior to and after respiratory therapy and use of inhaled albuterol in cystic fibrosis patients colonized with Pseudomonas aeruginosa

OBJETIVO: Avaliar se a fisioterapia respiratória seguida do uso de salbutamol inalatório modifica a deposição pulmonar de tobramicina inalatória em pacientes com fibrose cística (FC) e se a deposição pulmonar apresenta correlação com a gravidade da doença ou com o genótipo. MÉTODOS: Um estudo prospectivo foi realizado com pacientes com FC maiores de 6 anos e colonizados por Pseudomonas aeruginosa. Os critérios de exclusão foram exacerbação pulmonar, mudança terapêutica entre as fases do estudo e FEV1 < 25 por cento. Todos os pacientes foram submetidos à cintilografia pulmonar com câmara de cintilação com um colimador low energy all purpose para avaliar a penetração da droga após a inalação de tobramicina marcada com tecnécio (99mTc-tobramicina), e à perfusão pulmonar com 99mTc-macroagregados de albumina (fase 1). Após um mês, foi realizado o mesmo procedimento precedido de fisioterapia respiratória e administração de salbutamol inalatório (fase 2). RESULTADOS: Foram incluídos 24 pacientes (12 masculinos) com idade variando de 5 a 27 anos (média ± dp: 12,85 ± 6,64 anos). O escore de Shwachman (ES) foi excelente/bom em 8 pacientes, moderado/regular em 8 e grave em 0. A genotipagem revelou que 7 pacientes eram ΔF508 homozigotos, 13 eram ΔF508 heterozigotos, e 4 apresentavam outras mutações. A deposição pulmonar da tobramicina foi menor na fase 2 em todos os pacientes, sendo menor nos pacientes com ES moderado/regular (p = 0,017) e também nos heterozigotos (p = 0,043). CONCLUSÕES: O uso de uma técnica de fisioterapia respiratória e a administração de salbutamol inalatório imediatamente antes do uso de tobramicina inalada diminuem a deposição pulmonar desta última em pacientes com FC, e esta redução tem correlação com a gravidade da doença e genótipo.

OBJECTIVE: To evaluate whether respiratory therapy followed by the use of inhaled albuterol modifies the pulmonary deposition of inhaled tobramycin in patients with cystic fibrosis (CF) and whether pulmonary deposition correlates with disease severity or genotype. METHODS: A prospective study was carried out including patients with CF older than 6 years of age and colonized with Pseudomonas aeruginosa. Exclusion criteria were pulmonary exacerbation, changes in therapy between the study phases and FEV1 < 25 percent. All patients were submitted to pulmonary scintigraphy by means of a scintillation camera equipped with a low energy all purpose collimator in order to evaluate drug penetration following the administration of inhaled 99mTc-tobramycin, as well as to pulmonary perfusion with 99mTc-macroaggregated albumin (phase 1). One month later, the same procedure was performed following respiratory therapy and administration of inhaled albuterol (phase 2). RESULTS: We included 24 patients (12 males) aged 5-27 years (mean ± SD: 12.85 ± 6.64 years). The Shwachman score (SS) was excellent/good in 8 patients, moderate/fair in 16 and poor in 0. Genotyping revealed that 7 patients were ΔF508 homozygotes, 13 were ΔF508 heterozygotes; and 4 presented other mutations. In all patients, lung deposition of tobramycin decreased in phase 2, especially in those with moderate/fair SS (p = 0.017) and in heterozygotes (p = 0.043). CONCLUSIONS: The use of a respiratory therapy technique and the administration of inhaled albuterol immediately prior to the use of inhaled tobramycin decreased the pulmonary deposition of the latter in CF patients, and this reduction correlates with disease severity and genotype.

Utilidad del 99mTc-glutatión en la evaluación y estadiamiento de pacientes con linfoma / Utility of the scintigraphy with 99mTc-glutathione in the evaluation and to stage of patient with lymphomas

Para determinar la utilidad de la gammagrafía con 99mTc-glutatión en la evaluación y estadiamiento de pacientes con linfoma, estudiamos 38 pacientes (30 linfomas y 8 enfermedades benignas de los ganglios). La biopsia del ganglio constituyó el gold standard. Las variedades histológicas más frecuentes fueron la esclerosis nodular en los linfomas Hodking y el bajo grado de malignidad para el no Hoddking. Se adquirieron imágenes planas anteriores y posteriores de tórax, abdomen y pelvis tras la administración de 925-1110 MBq (20-30 mCi) de 99mTc-glutatión. La gammagrafía con 99mTc-glutatión mostró valores de sensibilidad, especificidad y exactitud de 93.3 por ciento, 87.5 por ciento y 92.1 por ciento, respectivamente. El valor predictivo positivo (VVP) fue 96.5 por ciento y el valor predictivo negativo (VPN) 77.7 por ciento. De un total de 89 regiones ganglionares estudiadas, el 99mTc-glutatión detectó el 94.3 por ciento. Conclusiones: La gammagrafía con 99mTc-glutatión pudiera resultar útil en la evaluación y estadiamiento de pacientes con linfoma.

To determine the utility of the scintigraphy with 99mTc-glutathione in the evaluation and to stage of patient with lymphomas, we studied 38 patients (30 lymphomas and 8 benign disease of the lymph node). The biopsy of the lymph node constituted the gold standard. Nodular sclerosis in the Hodking lymphomas and the low grade of malignancy for the non-Hoddking were the most frequent histology varieties. Static images of thorax, abdomen and pelvis were acquired after the administration of 925-1110 MBq (20-30 MCI) of 99mTc-glutathione. Scintigraphy with 99mTc-glutathione showed values of sensibility, specificity and accuracy of 93.3 percent, 87.5 percent y 92.1 percent, respectively. The predictive positive value was 96.5 percent and the predictive negative value was 77.7 percent. The 99mTc-glutathione detected 94.3 percent of the lymph node regions studied (89 regions in total with lymph node). Conclusions: The scintigraphy with 99mTc-glutathione could be useful in the evaluation and staging of patient with lymphoma.

Modificación de la biodistribución de los glóbulos rojos marcados con 99mtc en la anemia ferropénica / Alteration in the biodistribution of 99mTc-RBC in an animal model of ferropenic anemia

Objetivo: Evaluar la biodistribución de 99mTc-GR en un modelo animal de anemia ferropénica. Materiales y métodos: Se utilizaron ratas alimentadas con dietas con diferente contenido de Fe: grupo A (anemia severa, 6.5 ppm), grupo B (anemia moderada, 18 ppm) y grupo C (control, 100 ppm). Se realizó la marcación in vivo de los 99mTc-GR y se evaluó la EBM y su biodistribución a los 30 minutos y a las 24 horas en sangre, hígado, bazo, tracto gastrointestinal, riñones, corazón y pulmones. Los resultados se expresaron como concentración de actividad porcentual (CA por ciento). Resultados: En todos los grupos la EBM fue superior al 98 por ciento. Se observó un aumento de CA por ciento en bazo a las 24 horas en el grupo A, acompañado de una disminución de la CA por ciento del pool sanguíneo posiblemente por aumento del secuestro esplénico de los GR. En los tres grupos hubo un aumento de la CA por ciento en riñón a las 24 horas. Conclusión: La biodistribución de 99mTc-GR se ve modificada en la anemia ferropénica.

Aim: To evaluate the biodistribution of 99mTc-RBC in an animal model of ferropenic anemia. Materials and methods: We used rats which were fed with different iron contents diets: group A (severeanemia, 6.5 ppm), group B (moderate anemia, 18 ppm) and group C (control, 100 ppm). We performed the in vivo labeling of RBC and evaluated the labeling efficiency and the biodistribution at 30 minutes and 24 hours in blood, liver, spleen, gastrointestinal tract, kidneys, heart and lungs. The results were expressed as activity concentration percentage (CA percent). Results: In all groups the labeling efficiency was higher than 98 percent. We observed an increase of CA percent in spleen at 24 hours in the group A, followed by a decrease of CA percent in blood. This could be a consequence of an increase of splenic uptake of RBC. An increase in CA percent in kidney was obtained at 24 hours for all the groups. Conclusion: An alteration in the RBC biodistribution is observed in an animal model of ferropenic anemia.

Biodistribution of 99m technetium- labeled creatinine in healthy rats

The distribution of creatinine, one of the toxic guanidine compounds, in various tissues has not been studied in detail by using radiolabeled creatinine. Our objective was to investigate the biodistribution of creatinine labeled with 99m technetium (99mTc) by the stannous (II) chloride method in healthy male Wistar rats. Quality controls were carried out by radio thin layer chromatography, high-performance liquid chromatography, and paper electrophoresis. The labeling yield was 85 ± 2 percent under optimum conditions (pH 7 and 100 æg stannous chloride). Rats (N = 12) were injected intravenously with 99mTc-creatinine and their blood and visceral organs were evaluated for 99mTc-creatinine uptake as percent of the injected dose per gram wet weight of each tissue ( percentID/g). The lowest amount of uptake was detected in the brain and testis. When the rate of uptake was evaluated, only the kidney showed increasing rates of uptake of 99mTc-creatinine throughout the study. Kidneys showed the highest amount of uptake throughout the study (P < 0.001 compared to all other organs), followed by liver, spleen and lung tissue.

A computer program for single-injection tracer clearance from one, two, or many blood samples

A computer program based on a Bayesian statistical model has been developed for calculating tracer clearance from any number of plasma samples drawn at arbitrary time intervals. Bayesian prior parameters were calculated from clinical data for Tc99m-MAG3, Tc99m-EC, I131-OIH, Tc99m-DTPA, and Yb169-DTPA and then used to calculate clearance from prospective data. Clearance estimates using only one or two plasma samples were found to closely approximate the results of using multiple samples. When only one or a few samples are available, the program supplements the observed data by a Bayesian prior probability distribution (based on prior clinical measurements) to achieve agreement with multisample clearance. When many points are available, the observed data overwhelm the prior probability, and results approach those of conventional curve fitting but with less sensitivity to bad data points and less risk of fitting failure.

The effect of glucantime™ on the labeling of blood constituents with technetium-99m

OBJETIVO: A marcação de hemácias sangüíneas (C) com 99mTc é muito utilizada nos procedimentos diagnósticos na medicina nuclear. Drogas podem alterar este método de marcação e modificar a biodisponibilidade de radiofármacos. Neste trabalho, foi avaliada a influência de glucantime na marcação de elementos sangüíneos com 99mTc. MÉTODOS: Sangue foi retirado de ratos e incubado com glucantime. Adicionou-se cloreto estanoso e 99mTc. Após centrifugação, plasma (P) e (C) foram isolados. Amostras de P e C foram precipitadas com TCA 5 por cento, centrifugadas e separadas em frações solúveis (FS) e insolúveis (FI). Os percentuais de atividade total injetada (por cento ATI) em C, FI-P e FI-C foram calculados (p<0,05). RESULTADOS: O %ATI em C diminuiu, em relação ao controle, nas seguintes concentrações de glucantime (6,25 por cento;12,5 por cento; 25 por cento; 50 por cento; 100por cento), respectivamente: 94,06±1,29 (controle) para 77,15±2,79; para 76,68±1,88; para 75,15±2,79; para 72,64±4,40 e para 63,05±3,84. Em FI-C, o %ATI diminuiu, em relação ao controle, em todas as concentrações de glucantime (3,125 por cento; 6,25 por cento; 12, 5 por cento; 25 por cento; 50 por cento; 100 por cento), respectivamente: 93,34±1,18 (controle) para 78,81±2,76; para 74,76±4,82; para 74,02±5,32; para 64,35±4,82; para 62,81±1,97 e para 54,55±3,58. CONCLUSÕES: Este efeito provavelmente foi devido a produtos presentes nesta droga que podem se complexar com íons (Sn+2 e 99mTcO-4) ou ter um efeito direto ou indireto na concentração intracelular do íon estanoso.

Tumor retention and biodistribution studies of etoposide loaded tripalmitin nanoparticles after intratumoral administration in Dalton's Iymphoma tumor bearing mice

The objective of the present work is to study the biodistribution and tumor retention properties of etoposide (anticancer agent) and etoposide loaded tripalmitin nanoparticles (ETPL) after intratumoral administration in Dalton's lymphoma tumor bearing mice. ETPL nanoparticles were prepared by melt-emulsification and high pressure homogenization followed by spray drying technique. The nanoparticles were uniform and possessed 387 nm mean diameter and negative charge with excellent redispersibility in aqueous media. Radiolabeling of etoposide and ETPL nanoparticles with Technetium-99m (99mTc) resulted in complexes with high labeling efficiency and low radiocolloid formation. The labeled complexes showed good in vitro stability as indicated by low transchelation in presence of DTPA and cysteine and stability in human serum. Biodistribution and tumor retention studies were performed for etoposide and ETPL nanoparticles after intratumoral injection in mice bearing Dalton's lymphoma tumor. Etoposide experienced rapid clearance from the tumor, while the disposition of ETPL nanoparticles was slower. The tissue concentrations of ETPL nanoparticles increased with time (i.e. at 6h and 24h post injection) indicating its retention in tumor site for a longer time. Tumor retention of both etoposide and ETPL nanoparticles was studied upto 48h post injection. The tumor concentration of both etoposide and ETPL nanoparticles was high initially (8.57 percent and 41.8 percent injected dose at 0.5h post injection) and decreased with time (0.12 percent and 1.68 percent injected dose at 48h post injection). The concentration of etoposide rapidly declined from the tumor site while the tumor retention of ETPL nanoparticles was significantly higher than free etoposide (P < 0.001) at all the time points studied. The over all many fold higher tumor retention of ETPL nanoparticles (14 folds even at 48h post injection) compared to etoposide, coupled with lower tissue distribution signifies...