Added value of SPECT/CT in addition to whole-body scintigraphy augmented with prone lateral views in patients with well-differentiated thyroid carcinoma

Purpose: We aimed to determine the impact of SPECT/CT performed in addition to whole-­‐body scintigraphy augmented with prone lateral views in patients with well-­‐differentiated thyroid carcinoma. Methods and Materials: This retrospective study included 141 patients (87 female, 54 male, mean age 47 years) with well-­‐differentiated thyroid carcinoma (105 papillary, 31 follicular, 1 Hürthle cell and 4 poorly differentiated) treated with radioiodine therapy (1000-7400 MBq). Patients were referred for either first postsurgical therapy (n=76) or further treatment (n=65). Two nuclear medicine physicians interpreted the scans in consensus (first whole-­‐body scintigraphy with prone lateral view, then SPECT/CT) reporting abnormal iodine uptake in the thyroid bed, lymph nodes and distant metastasis. The corresponding ATA risk score was calculated for each patient before and after SPECT/CT, as well as change in disease extension Results: The analysis showed a difference between scintigraphy and SPECT/CT in n=17 lesions in 14 patients (9.9%): 12 were described as suspicious on scintigraphy and could be considered as benign on SPECT/CT (3 corresponded to local iodine uptake, 6 to lymph nodes metastases and 3 to distant metastases). The others 5 corresponded to metastases (4 lymph nodes and 1 distant) that were not seen on whole-­‐body scintigraphy augmented with prone lateral views. In 10 of 141 (7.1%) patients, we observed a change in ATA risk stratification, with a risk increase in 4 of them (2.8%). Conclusion: SPECT/CT allowed detecting 5 focal lesions missed on planar scintigraphy, and to precise benignity of 12 suspicious lesions on planar scintigraphy. Moreover, SPECT/CT improved the risk stratification in 10 patients with a significant change in the patient management

In vivo imaging of vascular adhesion protein 1 - preclinical studies with positron emission tomography

The golden standard in nuclear medicine imaging of inflammation is the use of radiolabeled leukocytes. Although their diagnostic accuracy is good, the preparation of the leukocytes is both laborious and potentially hazardous for laboratory personnel. Molecules involved in leukocyte migration could serve as targets for the development of inflammation imaging agents. An excellent target would be a molecule that is absent or expressed at low level in normal tissues, but is induced or up-regulated at the site of inflammation. Vascular adhesion protein-1 (VAP-1) is a very promising target for in vivo imaging, since it is translocated to the endothelial cell surface when inflammation occurs. VAP-1 functions as an endothelial adhesion molecule that participates in leukocyte recruitment to inflamed tissues. Besides being an adhesion molecule, VAP-1 also has enzymatic activity. In this thesis, the targeting of VAP-1 was studied by using Gallium-68 (68Ga) labeled peptides and an Iodine-124 (124I) labeled antibody. The peptides were designed based on molecular modelling and phage display library searches. The new imaging agents were preclinically tested in vitro, as well as in vivo in animal models. The most promising imaging agent appeared to be a peptide belonging to the VAP-1 leukocyte ligand, Siglec-9 peptide. The 68Ga-labeled Siglec-9 peptide was able to detect VAP-1 positive vasculature in rodent models of sterile skin inflammation and melanoma by positron emission tomography. In addition to peptides, the 124I-labeled antibody showed VAP-1 specific binding both in vitro and in vivo. However, the estimated human radiation dose was rather high, and thus further preclinical studies in disease models are needed to clarify the value of this imaging agent. Detection of VAP-1 on endothelium was demonstrated in these studies and this imaging approach could be used in the diagnosis of inflammatory conditions as well as melanoma. These studies provide a proof-of-concept for PET imaging of VAP-1 and further studies are warranted.

Protection of plasmid DNA by a Ginkgo biloba extract from the effects of stannous chloride and the action on the labeling of blood elements with technetium-99m

Ginkgo biloba extract (EGb) is a phytotherapeutic agent used for the treatment of ischemic and neurological disorders. Because the action of this important extract is not fully known, assays using different biological systems need to be performed. Red blood cells (RBC) are labeled with technetium-99m (Tc-99m) and used in nuclear medicine. The labeling depends on a reducing agent, usually stannous chloride (SnCl2). We assessed the effect of different concentrations of EGb on the labeling of blood constituents with Tc-99m, as sodium pertechnetate (3.7 MBq), and on the mobility of a plasmid DNA treated with SnCl2 (1.2 µg/ml) at room temperature. Blood was incubated with EGb before the addition of SnCl2 and Tc-99m. Plasma (P) and RBC were separated and precipitated with trichloroacetic acid, and soluble (SF-P and SF-RBC) and insoluble (IF-P and IF-RBC) fractions were isolated. The plasmid was incubated with Egb, SnCl2 or EGb plus SnCl2 and agarose gel electrophoresis was performed. The gel was stained with ethidium bromide and the DNA bands were visualized by fluorescence in an ultraviolet transilluminator system. EGb decreased the labeling of RBC, IF-P and IF-RBC. The supercoiled form of the plasmid was modified by treatment with SnCl2 and protected by 40 mg/ml EGb. The effect of EGb on the tested systems may be due to its chelating action with the stannous ions and/or pertechnetate or to the capability to generate reactive oxygen species that could oxidize the stannous ion.

Effect of oral ingestion of an extract of the herb Uncaria tomentosa on the biodistribution of sodium pertechnetate in rats

The aim of the present study was to determine the effect of the oral ingestion of an extract of the herb Uncaria tomentosa (cat's claw) on the biodistribution of the radiobiocomplex sodium pertechnetate (Na99mTcO4) in rats. The animals (male Wistar rats, 2 months old, 180-220 g), were treated (1 mL) with an U. tomentosa extract (32 mg/mL, N = 5) or 0.9% NaCl solution (control, N = 5) for 7 days. After this period, Na99mTcO4 (3.7 MBq, 0.3 mL) was injected through the ocular plexus and after 10 min the rats were killed, the organs isolated and counted in a well-gamma counter. A significant (P < 0.05) alteration in Na99mTcO4 uptake i) from 0.57 ± 0.008 to 0.39 ± 0.06 %ATI/organ (P < 0.05) and from 0.57 ± 0.17 to 0.39 ± 0.14 %ATI/g (P < 0.05) was observed in the heart, ii) from 0.07 ± 0.02 to 0.19 ± 0.07 %ATI/g in the pancreas, and iii) from 0.07 ± 0.01 to 0.18 ± 0.07 %ATI/g (P < 0.05) in muscle after treatment with this extract. Although these results were obtained with animals, caution is advisable in the interpretation of the nuclear medicine examination when the patient is using this herb. This finding is probably an example of drug interaction with a radiopharmaceutical, a fact that could lead to misdiagnosis of the examination in clinical practice with unexpected consequences for the patient.

Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [99mTc(MIBI)6]+

Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [99mTc(MIBI)6]+ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol:chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [99mTc(MIBI)6]+ since impurities such as99mTc-reduced-hydrolyzed (RH),99mTcO4- and [99mTc(cysteine)2]-complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

Neurocirugia radioguiada en los tumores cerebrales de alto grado, experiencia INC

La cirugía radioguiada es una rama de la medicina nuclear con la cual se marca el tejido tumoral con un radiotrazador (MIBI) y mediante el uso de una gamasonda o gamacámara poder diferenciarlo del tejido cerebral sano in vivo en la sala de cirugía. Esta técnica se ha aplicado con éxito en tumores del SNC (Gliomas de alto grado, metástasis, meningiomas). Los tumores del SNC representan el 1% de todos los tumores pero son la tercera causa de mortalidad por cáncer en el mundo. Hay un mejor pronóstico de los pacientes con mayor extensión de la resección. Objetivos: Evaluar la factibilidad de la técnica y optimizar los procesos en el INC con la finalidad de desarrollar un protocolo de línea de investigación en esta materia. Materiales y métodos: se realiza un reporte de casos de pacientes con diagnóstico de tumor cerebral supratentorial. Se realizó SPECT cerebral con MIBI para confirmar captación del radiotrazador. En los pacientes que marcaron positivo se programó cirugía radioguiada con gamacámara portátil Sentinel Resultados: En 5 pacientes con tumores supratentoriales se realizó SPECT cerebral con MIBI: 3 de ellos fueron positivos los cuales fueron programados para cirugía radioguiada y los 2 restantes con cirugía convencional. Dos de los casos positivos correspondieron a Tumor de alto grado y un caso de tumor abscedado. En quienes se practicó la cirugía radioguiada se consiguió resección tumoral completa tumoral por imagen de gamacámara intraquirúrgica

[177Lu – DOTA – Tyr3] – OCTREOTATE para el tratamiento de tumores neuroendocrinos gastroenteropancreáticos. Revisión sistemática de la literatura.

Introducción: los tumores neuroendocrinos gastroenteropancreáticos se diagnostican en estadio avanzado en 60 - 80% de los pacientes y las opciones terapéuticas son limitadas. Se realizó una revisión sobre el beneficio clínico del tratamiento con [177Lu - DOTA - Tyr3] - Octreotate en pacientes con enfermedad metastásica o inoperable. Objetivos: evaluar la eficacia, impacto en calidad de vida y toxicidad de la terapia con 177Lu DOTATE en pacientes con tumores neuroendocrinos gastroenteropancreáticos avanzados. Materiales y Métodos: se condujo una revisión sistemática de la literatura mediante la búsqueda de estudios clínicos prospectivos y retrospectivos en bases electrónicas (MEDLINE, EMBASE, LILACS, SCIELO, OVID y la Biblioteca Cochrane) de cualquier idioma, año y estado de publicación. Se incluyeron 5 estudios, por la heterogeneidad existente entre los estudios no se realizó un metaanálisis. Resultados: la respuesta tumoral global fue del 45 - 57%, la enfermedad permaneció estable en 27% - 38% y progresó en 6% - 21% de casos en las series incluidas. El tiempo libre de progresión osciló entre 31 - 40 meses y la sobrevida global de 31– 51 meses. Se observó toxicidad hematológica grado 3-4 hasta en 9.5% de pacientes. Hubo mejoría significativa en la calidad de vida de pacientes tratados con 177LuDOTATATE. Conclusiones: la terapia con 177Lu- DOTATATE ofrece un beneficio clínico a los pacientes con tumores neuroendocrinos bien diferenciados avanzados por su impacto positivo en calidad de vida, control de síntomas, ralentiza la progresión tumoral y su toxicidad es baja.

Biodistribution of technetium-99m pertechnetate after Roux-en-Y gastric bypass (Capella technique) in rats

The biodistribution of sodium pertechnetate, the most used radiopharmaceutical in nuclear medicine, has not been studied in details after bariatric surgery. The objective was to investigate the effect of Roux-en-Y gastric bypass (RYGB) on biodistribution of sodium pertechnetate (Na99mTc-) in organs and tissues of rats. Methods: Twelve rats were randomly divided into two groups of 6 animals each. The RYGB group rats were submitted to the Roux-en-Y gastric bypass and the control group rats were not operated. After 15 days, all rats were injected with 0.1mL of Na99mTc- via orbital plexus with average radioactivity of 0.66 MBq. After 30 minutes, liver, stomach, thyroid, heart, lung, kidney and femur samples were harvested, weighed and percentage of radioactivity per gram (%ATI/g) of each organ was determined by gama counter Wizard Perkin-Elmer. We applied the Student t test for statistical analysis, considering p<0.05 as significant. Results: Significant reduction in mean %ATI/g was observed in the liver, stomach and femur in the RYGB group animals, compared with the control group rats (p<0.05). In other organs no significant difference in %ATI/g was observed between the two groups. Conclusion: This work contributes to the knowledge that the bariatric surgery RYGB modifies the pattern of biodistribution of Na99mTc

Efeitos biológicos in vitro de agentes físicos utilizados em fisioterapia

The uses of radiobiocomplexes labeled with technetium-99m contributed to health science advances. Stannous chloride (SnCl2) has been used as a reducing agent for the labeling process. Cytotoxic and genotoxic effect of the SnCl2 have been described in several studies and with this experimental models alterations in molecular and cellular level can be evaluated. In the last years the physicals therapists acquired new devices which emits electromagnetic radiation such us Extremely Low Frequency Pulsated Electromagnetic Fields (E.L.F. P.E.M.F.), radiofrequency, Intense Pulsed Light (I.P.L.) and others which emits sonic waves such us Biorresonance. Scientific evidence of the effects and dosage is important to protect public health and to reach exposition levels that result in significant biological effects. The aim of this project is to verify the effects of these physical agents in plasmid DNA and E. coli AB1157 cultures in presence or absence of SnCl2 and the effects in blood constituents labeled with technetium-99m. Wistar rats blood was exposed to the cited sources and the labelling of blood constituents with 99mTc was carried through. Cultures of E. coli AB1157 and plasmidial samples DNA had been also exposed the physical agents. The results suggest that these agents are capable of altering neither the survival of E. coli cells or plasmid DNA electrophoresis mobility. The multidiscipline character was clearly in this study due the interaction between Nuclear Medicine department of the UERJ and the Laboratory of Physical Agents of the Maimonides University in Argentina until the union between the teacher (biomedical and physiotherapist) and student (physiotherapist), besides collaborators of the area of Physics and Biology, promoting new ideas and perspectives and also adding the knowledge of different areas and origins

Efeito de preparações de produtos naturais (cravo da índia e tomate) e de um produto sintético na marcação de constituintes sangüineos com tecnécio-99m e na morfologia de hemácias isoladas de sangue de ratos wistar

There are strong interests in the evaluation of the biological effects of natural and synthetic products. Blood constituents labeled with technetium-99m (99mTc) are used in nuclear medicine. The aim of this work was to study the effects of Clove (Caryophyllus aromaticas L.) and OZE (preparation used in the Health Sciences) on the labeling blood constituents with 99mTc and on the morphologic red blood cells (RBC) and the action of an extract of tomato (TO) on the labeling of blood constituents Blood samples were incubated with clove or OZE or TO, stannous chloride and 99mTc. Plasma (P), blood cells (BC), insoluble fractions (IF) of plasma and blood cells were separated. The radioactivity was counted and percentage of radioactivity (%ATI) to each blood fraction was calculated. The shape and morphometric parameter (perimeter/area ratio) were evaluated in the studies with clove and OZE. Clove extract and OZE altered significantly (p<0.05) the %ATI of blood constituents and the shape of red blood cells. However, clove extract not altered the red blood cells perimeter/area ratio. The tomato extract used at the highest concentrations reduced significantly (p<0.05) the %ATI in IF-P, although this extract did not modify the radiolabeling on BC, neither the radioactivity fixation on IFBC. The results indicate that these chemical compounds would have oxidative/chelating actions

Avaliação de efeitos de um extrato aquoso de cinnamomum zeylanicum L. na marcação de constituintes sanguíneos com tecnécio-99m e na morfologia das hemácias de ratos wistar

Radiobiocomplexes are used to obtain images in nuclear medicine and employed in basic research. Blood constituents labeled with technetium-99m (99mTc) have also been employed as radiobiocomplexes and used also experimental model for evaluation of the biological effects of natural or synthetic drugs. The analysis of the morphology and the morphometrics parameters (perimeter/área ratio) can be used to evaluate the effects of drugs upon the structure of the membrane of red blood cells. Cinnamomum zeylanicum (cinnamon) is a spice used as herbal medicine to treat diseases. The aim of this study was to evaluate the effect of in vitro and in vivo treatment with an aqueous cinnamon extract on the labeling of blood constituents with 99mTc and on the morphology of red blood cells from Wistar rats. In the in vitro treatment, isolated blood sample from animals were incubated with cinnamon extract. In the in vivo treatment, blood samples were also withdrawn from animals treated with cinnamon extract. In both cases, the radiolabeling of blood constituents was done. The morphological analysis of red blood cells was also done. As control, blood or animals treated with NaCl 0.9%. The data obtained on the labeling of blood constituents with 99mTc experiments indicated that the in vitro treatment with cinnamon extract was capable to decrease signiicantly (p<0.05) the percentage of radioactivity in cellular compartments and on the fixation of cellular and plasma proteins. These effects were not observed on the in vivo treatment. The results obtained for the morphology of red blood cells suggest that the in vitro and in vivo treatments did not alter the morphology and the perimeter/area ratio. The in vitro treatment with aqueous cinnamon extract could affect the membrane structures related with the oxidation status of the stannous ion pertechnetate ion, altering the labeling of blood constituentes with 99mTc. This study was a multidisciplinary experimental research. It was developed with the contribution of the different Departments and Services of the Hospital Universitário Pedro Ernesto of the Universidade do Estado do Rio de Janeiro

Estudo de efeitos de um extrato de Arctium lappa (Bardana) na marcação dos constituintes sangüíneos com Tecnécio-99m, na biodisponibilidade do radiofármaco pertecnatato de sódio e na morfologia de hemácias de ratos Wistar

Radionuclides have been used in Nuclear Medicine for diagnostic and treatment. In basic research, cellular and molecular structures are labeled with technetium-99m (99mTc) and used as radiobiocomplexes. Some natural or synthetic drugs are capable to alter the labeling of blood constituents with 99mTc, as well as in the biodistribution of radiobiocomplexes. Arctium lappa (Bardana) has been used to treat inflammatory processes. The aim of this work was to evaluate the effects of an extract of Bardana on the labeling of blood constituents with 99mTc, on the morphology of red blood cells, on the perimeter/area ratio of red blood cells and on the biodistribution of radiophamaceutical sodium pertechnetate in Wistar rats. Extract of Bardana was capable to alter the labeling of cellular compartment with 99mTc. Plasma and cellular proteins did not present alteration on the percentage of radioactivity (%ATI). Extract of Bardana was also capable to alter the morphology and the perimeter/area ratio of red blood cells. On the biodistribution of sodium pertechnetate in animals treated with the extract of Bardana, it was observed a small and significant uptake in liver, tooth and tongue, and a high and a significant uptake in stomach, lung and testis (p<0.05). In conclusion, these findings could be justified due to the effects of some chemical compounds in the Bardana extract. This study was a multidisciplinary experimental research. It was developed with the contribution of the different Departments and Services of the Hospital Universitário Pedro Ernesto of the Universidade Estadual do Rio de Janeiro

Estudo de efeitos de um extrato aquoso de farinha de casca de maracujá (Passiflora edulis f. flavicarpa) na marcação de constituintes sangüíneos com Tecnécio 99m, na morfometria das hemácias e na biodisponibilidade do radiofármaco Pertecnetato de Sódio em ratos Wistar

Blood constituents labelled with technetium-99m (99mTc) has been used with radiobiocomplexes in several procedures in nuclear medicine. Some natural and sintetic drugs are capable to interfere on the labeling of blood constituents with 99mTc, on the morphology of red blood cells (RBC) and on the biodistribution of radiobiocomplexes. The aim of this study was evaluate the effect of an extract of Passiflora edulis f. flavicarpa on the labeling of blood constituints with 99mTc, on the morphology of RBC and on the biodistribution of the radiopharmaceutical sodium perthecnetate in Wistar rats. On the in vitro studies the Passiflora edulis f. flavicarpa decreased significantly (p<0.05) the %ATI on plasma proteins and on the in vitro morhology of RBC, the passion fruit peel flour altered the shape and the perimeter/área ratio. On the in vivo estudies the extract did not altered the %ATI in blood constituents, and did not altered the shape of RBC. Although, on the biodistribution of the radiobiocomplex sodium perthecnetate (Na99mTcO4) this extract decreased significantly (p<0.05) the uptake in duodenum, spleen, pâncreas and blood, and increased the uptake in stomach. It can be suggested that the effects presented by this extract could be a result of some substances contained in this extract that could alter the binding of 99mTc to plasma proteins, the morphology of RBC and the biodistribution of the radiobiocomplex sodium perthecnetate. This study was multidisciplinary experimental research. It was developed with the contribution of different Departments and Services of the Hospital Universitário Pedro Ernesto of the Universidade Estadual do Rio de Janeiro

Efeito de um extrato de Artemísia Vulgaris L. marcação in vitro de constituintes sanguíneos com tecnécio-99m em ratos wistar

Artemisia vulgaris L..is used in folk medicine and in Traditional Chinese Medicine (TCM). This medicinal plant has been utilized as anticonvulsive, analgesic, antispasmodic effect, rheumatic pains, menstrual dyspepsia, asthenia, epilepsy, hepatitis, fevers, anemia and to expel parasites. In nuclear medicine, blood constituents are labeled with technetium-99m (99mTc) and used as radiopharmaceuticals (radiobiocomplexes). Authors have been described that synthetic and/or natural drugs could modify the labeling of blood constituents with 99mTc. The aim of this work was to evaluate the effects of an aqueous extract of Artemisia vulgaris L. on the labeling of blood constituents with 99mTc. Blood samples withdrawn of Wistar rats were incubated with Artemisia vulgaris L, stannous chloride and 99mTc, as pertechnetate ion. Aliquots of plasma (P) and blood cells (BC) were isolated. Aliquots of P and BC were also precipitated with trichloroacetic acid and soluble (SF) and insoluble (IF) fractions were separated. The radioactivity in each fraction was counted and the percentages of radioactivity (%ATI) were calculated. Artemisia vulgaris L. extract decreased significantly (p<0.05) the %ATI on BC and on IF-BC. The analysis of the results indicates that the extract could have substances that could interfere on the transport of stannous through the erythrocyte membrane altering the labeling of blood cells with 99mTc. Working in this study was a multidisciplinary group, with Phisical therapists, Biomedicals, Physicals, Pharmacists, Biologists, Statistics and Physicians.

Avaliação de efeitos DW extratos de sambucus australis E sambucus nigra na marcação de constituintes sanguineos com tecnécio-99M, na morfologia de Hemácias de ratos wistar, na topologia plasmidial e na ação do cloreto estanoso no DNA Plasmidial

Radiobiocomplexes are used in nuclear medicine to obtain images and to treat diseases. Blood constituents have been used as radiobiocomplexes. Natural or synthetic products can influence on the labeling of blood constituents with technetium-99m (99mTc), the morphology of red blood cells and on the stannous chloride (SnCl2) action on plasmid DNA. Sambucus australis and Sambucus nigra are used in popular culture for treating diseases. The aim of this work was to evaluate the effects of the extracts of Sambucus australis and Sambucus nigra on the labeling of blood constituents with 99mTc, on morphology of red blood cells of Wistar rats, on the topology of plasmids DNA and the action against the SnCl2 effects on the DNA of plasmids pBSK. On the labeling of blood constituents with 99mTc it was verified that both extracts were capable to decrease significantly the radioactivity in the cellular compartment and in the insoluble fraction of plasma. Sambucus australis also decreased the labeling of insoluble fraction of blood cells with 99mTc. Both extracts did not alter the morphology of red blood cells. Moreover, it was verified that Sambucus nigra did not alter the electrophoretic profile of plasmid DNA, but decreased the effect of SnCl2 on plasmid DNA. These last results sugest a genotoxic effect and a protective action of Sambucus nigra extract against the SnCl2 action on plasmid DNA. This work was developed with the contribution of several Departments of biomedical area of the Hospital Universitário Pedro Ernesto, of the UERJ, characterizing a multidisciplinary experimental research