Functional investigation of bone implant viability using radiotracers in a new model of osteonecrosis

OBJECTIVES: Conventional imaging methods are excellent for the morphological characterization of the consequences of osteonecrosis; however, only specialized techniques have been considered useful for obtaining functional information. To explore the affinity of radiotracers for severely devascularized bone, a new mouse model of isolated femur implanted in a subcutaneous abdominal pocket was devised. To maintain animal mobility and longevity, the femur was harvested from syngeneic donors. Two technetium-99m-labeled tracers targeting angiogenesis and bone matrix were selected. METHODS: Medronic acid and a homodimer peptide conjugated with RGDfK were radiolabeled with technetium-99m, and biodistribution was evaluated in Swiss mice. The grafted and control femurs were evaluated after 15, 30 and 60 days, including computed tomography (CT) and histological analysis. RESULTS: Radiolabeling achieved high (>95%) radiochemical purity. The biodistribution confirmed good blood clearance 1 hour after administration. For 99mTc-hydrazinonicotinic acid (HYNIC)-E-[c(RGDfK)2, remarkable renal excretion was observed compared to 99mTc-methylene diphosphonate (MDP), but the latter, as expected, revealed higher bone uptake. The results obtained in the control femur were equal at all time points. In the implanted femur, 99mTc-HYNIC-E-[c(RGDfK)2 uptake was highest after 15 days, consistent with early angiogenesis. Regarding 99mTc-MDP in the implant, similar uptake was documented at all time points, consistent with sustained bone viability; however, the uptake was lower than that detected in the control femur, as confirmed by histology. CONCLUSIONS: 1) Graft viability was successfully diagnosed using radiotracers in severely ischemic bone at all time points. 2) Analogously, indirect information about angiogenesis could be gathered using 999mTc-HYNIC-E-[c(RGDfK)2. 3) These techniques appear promising and warrant further studies to determine their potential clinical applications.

Radiolabeling of methanol extracts of yarrow (Achillea millefolium l) in rats / Radiomarcação do extrato metanólico de yarrow (Achillea millefolium l) em ratos

PURPOSE: Current study is focused on extraction with methanol, purification, labeling with 131I using iodogen method of the yarrow plant and investigating in vivo biological activity using biodistribution and imaging studies on healthy animal models. The aim of the study is to contribute plant extracts to discover new drugs in the diagnosis and treatment of several diseases. METHODS: Nine female and nine male healthy Wistar albino rats, which were approximately 100-150 g in weight, were used for biodistribution studies. For imaging studies four healthy male Balb-C mice were used. Quality control studies were done utilizing thin layer radio chromatography (TLRC) and high performance liquid chromatography (HPLC) methods. For biodistribution studies, 131I radiolabeled Peak 7 (131I-Peak 7) was sterilized and injected into the tail veil of rats and imaging studies were obtained using Kodak FX PRO in vivo Imaging System. RESULTS: The radiolabeling yield of each purified the bioactive extracts of the yarrow plant, seven peaks was between 79 and 92%. The highest radiolabeling yield was calculated for 131I radiolabeled seventh peak (131I-Peak 7) (92.78±5.04, n=5). For this reason the biodistribution and imaging studies were done for 131I-Peak 7. That's why; these studies with Peak 7 were carried out. CONCLUSION: Peak 7 was radiolabeled with 131I in high yield for using imaging and therapeutic studies in nuclear medical applications.

OBJETIVO: O atual estudo tem por objetivo a extração com metanol, purificação, marcação com I131 usando o método direto de marcação da planta Achillea, para investigar in vivo a atividade biológica usando biodistribuição e estudos de imagem em modelos animais saudáveis. O objetivo do estudo é contribuir com extratos de plantas para descobrir novas drogas para o diagnóstico e tratamento de várias doenças. MÉTODOS: Nove fêmeas e nove machos ratos Wistar albino saudáveis, com aproximadamente 100 a 150g de peso foram usados para estudos de biodistribuição. Para estudos de imagem, quatro camundongos Balb-C machos e saudáveis foram usados. Estudos de controle de qualidade foram realizados usando métodos de cromatografia de camada fina e cromatografia líquida de alta performance. Para estudos de biodistribuição, pico 5 radiografado com I131 (I131-Peak 7) foi esterilizado e injetado na veia da cauda dos ratos e estudos de imagem foram obtidos usando Sistema de Imagem Kodak FX PRO in vivo. RESULTADOS: O retorno radiomarcado de cada extrato bioativo purificado da planta Achillea sete picos estavam entre 79 e 92%. O retorno com maior marcação foi calculado para I131 sétimo pico (I131-Peak 7) (92,78±5,04, n=5). Por esta razão os estudos de biodistribuição e de imagem foram feitos para I131-Peak 7. CONCLUSÃO: Peak 7 foi radiomarcado com I131 em alto retorno para uso em estudos terapêuticos e de imagens nas aplicações médicas nucleares.

Comparison of two peptide radiotracers for prostate carcinoma targeting

OBJECTIVES: Scintigraphy is generally not the first choice treatment for prostate cancer, although successful studies using bombesin analog radiopeptides have been performed. Recently, a novel peptide obtained using a phage display library demonstrated an affinity for prostate tumor cells. The aim of this study was to compare the use of a bombesin analog to that of a phage display library peptide (DUP-1) radiolabeled with technetium-99m for the treatment of prostate carcinoma. The peptides were first conjugated to S-acetyl-MAG3 with a 6-carbon spacer, namely aminohexanoic acid. METHODS: The technetium-99m labeling required a sodium tartrate buffer. Radiochemical evaluation was performed using ITLC and was confirmed by high-performance liquid chromatography. The coefficient partition was determined, and in vitro studies were performed using human prostate tumor cells. Biodistribution was evaluated in healthy animals at various time points and also in mice bearing tumors. RESULTS: The radiochemical purity of both radiotracers was greater than 95 percent. The DUP-1 tracer was more hydrophilic (log P = -2.41) than the bombesin tracer (log P = -0.39). The biodistribution evaluation confirmed this hydrophilicity by revealing the greater kidney uptake of DUP-1. The bombesin concentration in the pancreas was greater than that of DUP-1 due to specific gastrin-releasing peptide receptors. Bombesin internalization occurred for 78.32 percent of the total binding in tumor cells. The DUP-1 tracer showed very low binding to tumor cells during the in vitro evaluation, although tumor uptake for both tracers was similar. The tumors were primarily blocked by DUP1 and the bombesin radiotracer primarily targeted the pancreas. CONCLUSION: Further studies with the radiolabeled DUP-1 peptide are recommended. With further structural changes, this molecule could become an efficient alternative tracer for prostate tumor diagnosis.

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.

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.

Marcaje indirecto de anticuerpos monoclonales empleando la N2-dietilentriamino-pentaacetil lisina amida como agente quelatante del 99mTc / Indirect labeling of monoclonal antibodies with 99mTc, using N2-diethylentriamine-pentaacetil lysine amide as chelating agent

Los anticuerpos monoclonales y sus fragmentos marcados se han empleado ampliamente en el diagnóstico y seguimiento de diferentes tipos de neoplasias. El objetivo del trabajo fue desarrollar una metodología para el marcaje indirecto de anticuerpos con 99mTc, partiendo de la N2-dietilentriamino-pentaacetil lisina amida como agente quelatante. Mediante reacción con un exceso molar de 2-iminotiolano (1:200) y reducción con un exceso de 2-mercaptoetanol (1:2000) se generaron en el anticuerpo 3.5 +/- 0.6 y 5.8 +/- 0.5 grupos –SH, respectivamente, por lo que se continuó el trabajo con la segunda metodología. Se incubó el h-R3 reducido durante 12 h con N6-ciclohexilmaleimido-N2-dietilentriaminopentaacetil lisina amida, obtenida previamente mediante la reacción de la N2-dietilentriamino-pentaacetil lisina amida con sulfosuccinimidil–4(N-maleimido-metil) ciclohexano-1-carboxilato de sodio. La eficiencia de marcaje con 99mTc del anticuerpo monoclonal h-R3 modificado según este método fue de (98.6 +/-1.4) por ciento, manteniendo una estabilidad satisfactoria hasta 24 h frente al exceso de L-cisteína (1:300). Conclusiones: La metodología desarrollada permitió el marcaje indirecto del anticuerpo monoclonal humanizado h-R3 con 99mTc de forma satisfactoria, empleando la N2- dietilentriaminopentaacetil lisina amida como agente quelatante bifuncional.

Labeled monoclonal antibodies and their fragments are been widely employed for the diagnosis and follow up of different kinds of neoplasm. The aim of the present work was to develop a method for indirect labeling of antibodies with 99mTc, using N2-diethylentriamine-pentaacetil lysine amide as chelating agent. By reactions with a 200-fold molar excess of 2-iminothiolane, and the reduction using a 2000-fold molar excess of 2-mercaptoethanol, 3.5 +/- 0.6 and 5.8 +/- 0.5 sulfhydril groups, respectively, were generated in the antibody. Thus, work was continued using the second procedure. Reduced h-R3 was incubated for 12 h with N6-cyclohexylmaleimide-N2-diethylentriamine-pentaacetil lysine amide, previously obtained by the reaction of N2-diethylentriamine-pentaacetil lysine amide with sodium sulfosuccinimidyl–4(N-maleimidomethyl)cyclohexane-1-carboxylate. Labeling efficiency of h-R3 monoclonal antibody, modified by this method with 99mTc, was (98.6 +/- 1.4) percent. A satisfactory stability of the label was observed up to 24 h in presence of a 300-fold molar excess of L-cysteine. Conclusions: Developed procedure allowed satisfactory indirect labeling of the humanized monoclonal antibody h-R3 with 99mTc, using N2-diethylentriamine-pentaacetil lysine amide as bifunctional chelating agent.

Gallium-68 (68Ga); the revival of an old positron emission tomography (PET) agent: the leading experience in Chile

In January 2008, we set up a 68Ge/ 68Ga generator able to produce enough quantities of 68Ga to label the same polypeptides, somatostatin analogos, used to treat patients suffering from neuroendocrine tumors. As far as we know, this is the first time that such a device is installed in Latin-America for specific PET/CT imaging different from 18F. During the last three months we have studied 30 patients for staging, re-staging and treatment control of neuroendocrine tumors using PET/CT images with 68Ga-DOTATATE. In all cases the image quality was excellent, providing clinically useful information in most of them. 68Ga is a very promising positron emitter radionuclide, cyclotron-independent, to label peptides and other molecules that open a wide window for Molecular Imaging.

En Enero de 2008 instalamos un generador de 68Ge/ 68Ga capaz de producir cantidades suficientes de 68Ga para marcar los mismos péptidos, análogos de la somatostatina, utilizados para el tratamiento de pacientes con tumores neuroendocrinos. De acuerdo con nuestro conocimiento, esta es la primera vez que se utilizada este aparato en Latinoamérica para obtener imágenes PET/CT específicas con un agente diferente al 18F. Durante los últimos tres meses hemos estudiado 30 pacientes con tumores neuroendocrinos con 68Ga-DOTATATE para etapificación, re-etapificación y control de tratamiento mediante imágenes PET/CT. En todos los casos la calidad de la imagen fue excelente proporcionando información clínicamente útil en la mayoría de ellos. 68Ga es un promisorio radionucleido emisor de positrones, independiente de un ciclotrón, para marcar péptidos y otras moléculas abriendo una amplia ventana para las Imágenes Moleculares.

Un estudio completo sobre la obtención de 99mTc-UBI 29-41 y su comportamiento in vitro e in vivo: su potencial uso en imágenes de infecciones / A complete study about the procurement of 99mTc-UBI 29-41 and its in vitro and in vivo behaviour: potential use in infection imaging

El objetivo del presente trabajo es investigar como se modifica el comportamiento in vitro e in vivo (localización de sitios de infección experimental con Staphilococcus aureus (S.a.)) del UBI 29-41 cuando es marcado con 99mTc por cuatro métodos distintos: a) con borohidruro de potasio y pirofosfato de estaño, b) con hidróxido de sodio y cloruro estañoso (métodos directos), c) con NHS-MAG3 y d) con NHS-HYNIC (métodos indirectos). En segundo lugar comparar los valores PI/PN (Pata Infectada / Pata Normal) del 99mTc-UBI 29-41 (método a), con el 99mTc-scrambled (Sc) UBI 29-41 (péptido control) y con 99mTc-IgG (radiofármaco no específico para infecciones) en ratones infectados con S.a. viables; y los valores pata inflamada/ PN del 99mTc-UBI 29-41 99mTc (método a) con 99mTc-IgG en ratones con inflamación estéril. Cuando el 99mTc-UBI 29-41 fue obtenido por el método a, se obtuvieron los mejores resultados in vitro y las biodistribuciones mostraron la máxima acumulación en sitios con S.a. viables y muy baja acumulación en sitios con inflamación estéril, demostrando su potencial uso en el diagnóstico de infecciones.

Factors affecting chemistry of reduction-mediated 99mTc-labelling of monoclonal antibodies and polyclonal human immunoglobulins.

In developing a new method for preparing a radiopharmaceutical for clinical investigation, a thorough understanding of reaction stoichiometry is crucial in optimizing the labelling chemistry. Factors determining labelling efficiency of the 2-mercaptoethanol (2-ME)-mediated 99mTc-labelling of antibody molecules were elucidated using anti-tumor monoclonal antibodies of different IgG subclasses (i.e. IOR-CEA(IgG1), M170(IgG1), 3F8(IgG3) and EMD (IgG2a)) and polyclonal human immunoglobulins (Sandoglobulin). Antibodies which were sensitive to 2-ME reduction (i.e. required 500-1000 molar excess of 2-ME) could tag 99mTc with high efficiency since they possessed abundant reactive sites (i.e. sulfydryl groups) for 99mTc binding. Reduction sensitivity of antibodies was unlikely to be affected by IgG subclass and could be rated as follows: Sandoglobulin > IOR-CEA > 3F8 > M170 > EMD. Concentrations of the reduced antibodies for effective labelling appeared to be related to the reduction sensitivity, i.e. 0.2, 0.4 and 0.6 mg/ml were required for labelling of IOR-CEA, 3F8 and M170 respectively. In addition, susceptibility to 2-ME reduction seemed to reflect the rate of antibody labelling. For 2-ME resistant molecules, i.e. M170 and EMD, successful labelling could be achieved by using a slow 99mTc reducing agent such as SnCl2 instead of SnF2 which reacted more rapidly. Since 2-ME generates reactive sulfhydryl groups that are distal to antigen binding sites, the immunoreactivity of the modified antibody was not affected by the effect of reduction.

Reduction-mediated 99mTc-labeling of antitumor monoclonal antibodies: effect of increasing specific activity on antibody binding kinetics.

Reduction-mediated 99mTc-labeling of antibodies has gained widespread acceptance in preparation of tumor imaging agents. Increased specific activity to enhance detection signals has raised the question of whether such an attempt would cause change in antibody binding kinetics. To answer this question, two antitumor monoclonal antibodies, i.e. IOR-CEA (IgG1) and EMD (IgG2a) were labeled with 99mTc to yield specific activities ranging from 549-4414 MBq/mg. Regression analysis of the binding data revealed that the binding kinetics of IOR-CEA were shifted from monovalent to bivalent binding upon increasing the specific activities. This phenomenon of affinity enhancement was confirmed by the dissociation study where we found soluble CEA had greater difficulty in extracting the cell-bound IOR-CEA labeled at higher specific activity. The bivalent bindings was further supported by the finding that IOR-CEA with higher specific activities delivered less than expected radioactivity to tumor targets despite their immunoreactivities being well preserved. For EMD, the kinetics seemed to be shifted from bivalent to monovalent interaction. At higher specific activities, adverse changes in immunoreactivity were recognized. Breakage of EMD into 99mTc-Fab fragments was likely to occur and was supported by the observation that EMD delivered more than expected radioactivities to target cells upon increasing specific activity. Precaution should be taken when one deals with high specific activity labeling since this might alter the antibody binding kinetics either favorably or unfavorably.

Marcação de estruturas biológicas com tecnécio-99m

A marcação de hemácias com 99mTc é dependente de vários fatores. como a concentração de íon estanoso, o tempo e temperatura de incubação, 0 tipo de anticoagulante utilizado, a presença de proteínas plasmáticas entre outros. A concentração de íon estanoso parece ter grande relevância, por que, provavelmente, devido a hemácia não ter capacidade para incorporar indefinidamente este íon depois de determinada concentração limitada pela saturação do mecanismo responsável por esta captação. 0 excesso de agente redutor que permanece no meio extra-celular contribui para a marcação de proteínas plasmáticas com o radionucl ídeo em questão. Além de mecanismo ativo responsável pela captação do íon estanoso, um transporte passivo, não dependente de energia deve estar também associado devido a 500C ser observada alta incorporação de radioatividade nas hemácias. As ligações do 99mTc com a hemoglobina e as proteínas plasmáticas apesar de serem similares, estas devem ter características próprias como demonstrado pelas precipitações com álcool, acetona , TCA, HC1 e cloreto mercuroso. A heterogeneidade das proteínas plasmáticas poderia ser responsável por estes resultados. As modificações ocasionadas nas hemácias pelo aquecimento a 50°C e os resultados experimentais obtidos neste trabalho permitiram desenvolver um "kit" e técnica para realização de cintigrafia esplênica seletiva de maneira muito simples e com pouca manipulação. O 99mtc, em decorrência dos resultados obtidos com bactérias, pode ser um radionuclídeo alternativo para a marcação de culturas bacterianas. As preparações bacterianas. marcadas em concentração ótima de cloreto estanoso, apresentam uma grande estabilidade da marcação. não alteração da viabilidade assim como não modificação da mobilidade eletroforética. Hidrofobicidade, distribuição de ferritina catiônica e adesividade às celulas bucais . A fração protéica e, mais precisamente a lipoproteica parece ser a espécie molecular que fixa de maneira substancial 0 radionuclídeo utilizado no processo de marcação de bactérias com 99mtc como demonstrado pela grande sensibil idade a ação de enzima pronase e detergente Triton X-100

The labeling of red blood cells (RBC) with technetium-99m (99mTc) depends on several factors, as the stannous ion (Sn++) concentration, the time and temperature of incubation, the anticoagulant utilized, the presence of plasma proteins (PP) and others. However the Sn++ concentration seems to be the most important factor, probably, because the uptake of this reducing agent by RBC is limited. The excess of Sn++ in extra-cellular medium can determine the label ing of the PP. An active transport of Sn++ through the membrane, and also a passive mechanism, probably can be involved, because at 50°c the incorporat ion of 99mTc by RBC is still observed. Although the binding of 99mTc with hemoglobin and PP are similar, they appear to have specific characteristics as demonstrated by precipitat ion with alcohol, acetone, trichloroacetic acid, hydrochloric acid and mercury chloride. The heterogeneity of PP can be responsable for this fact. The modifications of RBC at 50° C described in the literature, the possibility of labeling the RBC with 99mTc at this temperature and the experimental results obtained made it possible to develop a kit and a procedure to perform spleen selective scint igraphy through a simple technique and with few manipulations. Due to the results obtained labeling bacteriae with 99mTc, this radionuclide can be an alternative to this purpose. The bacterial cultures labeled with Technitium-99m, at optimal Sn++ ion concentration, present a large stability and their viabil ity is not altered by this treatment. The electrophoretic mobility, the hydrophobicity, the cat ionized ferritin distribut ion and the adherence to human buccal epithelial cells are not modified too. The protein fraction and mainly the lipoproteins appear to be the molecule that fixed the radionucltide in this process. This is demonstrated by the sensibil ity of this fract ion to the enzyme pronase and the detergent Triton X-100. The possibility of labeling with 99mTc of planaria and cercariae of Schistossoma mansoni evolutive cycle increases the utilization of this radionuclide to an experimental level. The results described with the labeling of theses biological structures with 99mTc demonstrated that stable labeled and viable preparations are obtained

Un método rápido y efectivo de marcaje de microesferas de albúmina con 113m In y 99mTc / An effective and rapid method for labeling albumin microspheres with 113m In and 99mTc

Se elaboró un método de marcaje de microesferas (mic A) con 113mIn y 99mTc. Se determinó el PH óptimo de marcaje, la influencia de la cantidad de Tween 80 y de cloruro estannoso (SnCl2, H2O), y el tiempo óptimo y mínimo de calentamiento y agitación. Los radiofármacos 99mTc-Sn-micA y 113m In-Sn-micA preparados por el método elaborado tienen pureza radioquímica mayor del 95. La introducción de este método dará la posibilidad de preparar los radiofármacos mencionados sin necesidad de importarlos

La preparación de radiofármacos, marcados con radionúclidos de iodo: I. Un método rápido de producción de ácido o-iodohippúrico-131I / Preparation of iodoradionuclides labelled radio-pharmaceuticals: I. A rapid method for the production of o-iodohippuric-131I acid

Se estudia la reacción de intercambio isotópico o-iodohippúrico y ioduro-131I de sodio, con el objetivo de la obtención de un KIT, a partir del cual se produce el radiofármaco hippuran-131I, utilizando Na 131I de baja actividad específica. Este radiofármaco se usa para determinar el funcionamiento renal. Se investiga la influencia de diferentes parámetros en el desarrollo de la reacción descrita anteriormente. Se realiza control de pureza radioquímica del radiofármaco, sus biodistribución y renograma en animales. Se encuentra que el aumento de la concentración del catalizador de la reacción aumenta la velocidad del intercambio. Además, el tiempo en que se termina el marcaje de ácido o-iodohippúrico depende de la cantidad del complejo intermediario formado del mismo con los iones CU+. Se obtiene el hippuran-131I a partir del KIT prescrito con Na 131I de baja actividad especifica con susficiente pureza radioquímica y rendimiento. Los estudios en animales señalan que el radiofármaco obtenido tiene un comportamiento similar que el hippuran-131I, actualmente usado en Cuba, procedente de la URSS. La aplicación de nuestro trabajo investigativo dará la posibilidad de desarrollar la producción propia de dicho radiofármaco en Cuba sin necesidad de importarlo