Sebastião David Santos-Filho

Drug interaction with radiopharmaceuticals: a review

Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes) and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99mT, can also be modified. These factors include drugs (synthetic and natural) and dietary conditions, as well as some medical procedures (invasive or non-invasive), such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemoperfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.

Acupuncture at "Zusanli" (St.36) and "Sanyinjiao" (SP.6) Points on the Gastrointestinal Tract: A Study of the Bioavailability of (99m)Tc-Sodium Pertechnetate in Rats.

The objective of this study is to investigate the differences of acupuncture effect between the Zusanli (St.36) and Sanyinjiao (SP.6) points on the gastrointestinal-tract (GIT) segment performed by the bioavailability of 99mTc-sodium-pertechnetate (Na99mTcO4) in rats. Male Wistar rats (n = 21) were allocated into three groups of seven each. Group 1 was treated by acupuncture bilaterally at St.36; Group 2 at SP.6; and Group 3 was untreated (control). After 10 min of needle insertion in anesthetized rats, 0.3 mL of Na99mTcO4 (7.4 MBq) was injected via ocular-plexus. After 20 min, the exitus of animals was induced by cervical-dislocation and GIT organs isolated. However, immediately before the exitus procedure, blood was collected by cardiac-puncture for blood radio-labeling (BRL). The radioactivity uptake of the blood constituents was calculated together with the GIT organs by a well gamma counter. The percentage of injected dose per gram of tissue (%ID/g) of Na99mTcO4 was calculated for each GIT organs, while BRL was calculated in %ID. According to the one-way ANOVA, the stomach, jejunum, ileum from the treated groups (Group 1 and Group 2) had significant differences compared to the controls (Group 3). However, between the treated groups (Group 1 and Group 2), there were significant differences (P < .05) in the stomach, jejunum, ileum, cecum, transverse and rectum. In BRL analysis, Group 2 showed significant increase and decrease of the insoluble and soluble fractions of the blood cells, respectively (P < .0001). The authors suggest that St.36 may have a tendency of up-regulation effect on GIT, whereas SP.6, down-regulation effect. However, further rigorous experimental studies to examine the effectiveness of acupuncture in either acupuncture points need to be carried out.

Effect of an extract of Centella asiatica on the biodistribution of sodium pertechnetate (Na99mTcO4) and on the fixation of radioactivity on blood constituents

This study evaluates the effects of an acute treatment with a Centella asiatica (CA) extract on the biodistribution of the radiopharmaceutical Na99mTcO4 and on the fixation of technetium-99m on blood constituents. Wistar rats were treated with CA extract and, 1 hour after, Na99mTcO4 was administered; organs/tissues were withdrawn and weighted. The radioactivity was counted to calculate the percentage of activity per gram (%ATI/g). Also, blood samples were withdrawn, plasma (P), blood cells (BC), insoluble fraction (IF) and soluble fractions of P and BC were isolated and the radioactivity was counted to calculate the percentage of activity (%ATI). Data indicated that the acute treatment with CA extract changed significantly (p<0.05) the %ATI/g in several organs/tissues (spleen, heart, duodenum, stomach, liver, muscle, kidney, testis and blood) and the %ATI on the blood constituents (P, BC, IF-P and IF-BC). These results indicate that the substances or metabolites of the CA extract would change the biodistribution of Na99mTcO4 and the fixation of the technetium-99m on blood constituents in an acute treatment.

Evaluation of Deoxyribonucleic Acid Toxicity Induced by the Radiopharmaceutical 99mTechnetium-Methylenediphosphonic Acid and by Stannous Chloride in Wistar Rats

Radiopharmaceuticals are employed in patient diagnostics and disease treatments. Concerning the diagnosis aspect, technetium-99m (99mTc) is utilized to label radiopharmaceuticals for single photon computed emission tomography (SPECT) due to its physical and chemical characteristics. 99mTc fixation on pharmaceuticals depends on a reducing agent, stannous chloride (SnCl2) being the most widely-utilized. The genotoxic, clastogenic and anegenic properties of the 99mTc-MDP(methylene diphosphonate used for bone SPECT) and SnCl2 were evaluated in Wistar rat blood cells using the Comet assay and micronucleus test. The experimental approach was to endovenously administer NaCl 0.9% (negative control), cyclophosphamide 50 mg/kg b.w. (positive control), SnCl2 500 μg/mL or 99mTc-MDP to animals and blood samples taken immediately before the injection, 3, and 24 h after (in the Comet assay) and 36 h after, for micronucleus test. The data showed that both SnCl2 and 99mTc-MDP-induced deoxyribonucleic acid (DNA) strand breaks in rat total blood cells, suggesting genotoxic potential. The 99mTc-MDP was not able to induce a significant DNA strand breaks increase in in vivo assays. Taken together, the data presented here points to the formation of a complex between SnCl2 in the radiopharmaceutical 99mTc-MDP, responsible for the decrease in cell damage, compared to both isolated chemical agents. These findings are important for the practice of nuclear medicine.

Ginkgo biloba extract alters the binding of the sodium [123I] iodide (Na123I) on blood constituents

We evaluated the in vitro effect of an aqueous extract of Ginkgo biloba (EGb) on the distribution in blood cells (BC) and plasma (P) and on the binding of Na(123)I to the blood constituents using precipitation with trichloroacetic acid. The radioactivity percentages insoluble (SF) and insoluble fraction (IF) of blood constituents were determined. The EGb interfered (p<0.05) on the distribution of Na(123)I in the P (from 69.64 to 86.13) and BC (from 30.36 to 13.87) and altered the fixation of the Na(123)I in IF-P and in IF-BC.

Lymphoscintigraphy in breast cancer: a short review about the impact on upper limb after surgical treatment

Breast cancer is still associated with high mortality rates and one of the most important factors governing long survival is accurate and early diagnosis. In underdeveloped countries, this disease frequently is only detected in advanced stages; however, through mammography, many women have been diagnosed at early stages. In this context, the sentinel lymph node (SLN) technique is associated with less postoperative morbidity compared to axillary lymphadenectomy. Lymphoscintigraphy has emerged as a method for the evaluation of lymphatic drainage chains in various tumours, being both accurate and non invasive. The aim of this work is to present the main aspects which cause controversy about SLN and lymphoscintigraphy and the impact that these procedures have had on lymphedema after surgical treatment for breast cancer. A short review including papers in English, Spanish and Portuguese, available on Lilacs and Medline database, published between January, 2000 and July, 2008 was performed. The key words breast cancer, lymphoscintigraphy, SLN biopsy, lymphedema were used. Various studies have aimed to compare the incidence and prevalence of lymphedema according to the technique used; however, the population subjected to SLN is different from the one with indication for axillary lymphadenectomy regarding staging. Moreover, little is known about long term morbidity since it is a relatively new technique. In conclusion, the development of surgical techniques has permitted to minimize deformities and the current trend is that these techniques be as conservative as possible. Thus, lymphoscintigraphy plays an important role in the identification of SLN, contributing to the prevention and minimization of postoperative complications.

Effect of an extract of Artemisia vulgaris L. (Mugwort) on the in vitro labeling of red blood cells and plasma proteins with technetium-99m

The aim of this work was to evaluate the effect of an extract of the Artemisia vulgaris L. (mugwort) on the labeling of blood constituents with technetium-99m (99mTc). Blood samples from Wistar rats were incubated with a mugwort extract and the radiolabeling of blood constituents was carried out. Plasma and blood cells were separated by centrifugation. Aliquots of plasma and blood cells were also precipitated with trichloroacetic acid and centrifuged to isolate soluble and insoluble fractions of plasma and blood cells. Radioactivity in each fraction was counted and the percentages of radioactivity (%ATI) was calculated. Mugwort extract decreased significantly (p<0.05) the %ATI on the blood compartments and on the blood cells proteins (insoluble fraction). The analysis of the results indicates that the extract could have substances that could interfere on the transport of stannous through the erythrocyte membrane alterating the labeling of blood cells with 99mTc.

Effects of Chrysobalanus icaco on the labeling of blood constituents with technetium-99m and on the shape of the red blood cells

Chrysobalanus icaco (abajeru; C.icaco) is recommended in the treatment of diabetes and other clinical disorders. Blood constituents labeled with technetium-99m (99mTc) are used in nuclear medicine. The aim of this study was to verify the effects of an abajeru extract on the labeling of blood constituents with 99mTc and on the shape of red blood cells (RBC). Blood samples(Wistar rats) were incubated with abajeru extract and the labeling of blood constituents with 99mTc and morphology of RBC were carried out. The results showed significant (P<0.05) alteration of labeling of blood constituents with 99mTc and the morphometry (perimeter/area ratio) of the RBC in presence of the extract. These data suggest that this abajeru extract could alter the labeling of blood constituents with 99mTc by its chelating/antioxidant action and/or effects on membrane structures involved in the ion transport.

Influence of whole-body vibration on biodistribution of the radiopharmaceutical [99mTc]methylene diphosphonate in Wistar rats

Abstract Purpose: The radionuclide bone scan is the basis of skeletal nuclear medicine imaging. Bone scintigraphy is a highly sensitive method for indicating disease in bone. Mechanical stimulation in the manner of whole-body vibration (WBV) appears beneficial to the maintenance and/or enhancement of skeletal mass in individuals. The aim of this work was to evaluate the effect of WBV on the biodistribution of the radiopharmaceutical [99mTc]methylene diphosphonate (99mTc-MDP ) in Wistar rats. Materials and methods: In the biodistribution analysis, animals were anesthetized with sodium thiopental, the radiopharmaceutical 99mTc-MDP was administered via ocular plexus and after 10 min the animals were submitted to vibration of 20 Hz (1 min) in an oscillatory platform. Following, the animals were sacrificed, the organs were isolated, the radioactivity determined in a well counter, and the percentages of radioactivity per gram (%ATI/g) in the organs were calculated. An unpaired t-test following Welch test (p < 0.05) was done for statistical analysis of the results. Results: The biodistribution was significantly (p < 0.05) decreased in kidney, bone, lung, stomach, prostate and bowel. Conclusion: The analysis of the results indicates that the vibration could produce metabolic alterations with influence in the uptake of the radiopharmaceutical 99mTc-MDP in bone, stomach, bowel, prostate, kidney and bladder.

Influence of an extract of Juglans regia on the growth of Escherichia coli, on the electrophoretic profile of plasmid DNA and on the radiolabeling of blood constituents

O objetivo desse trabalho foi estudar a influencia de um extrato de nogueira (Juglans regia) no crescimento de Escherichia coli (E. coli) AB1157, na topologia do DNA plasmidial e na marcacao de constituintes sanguineos com tecnecio-99m (99mTc). Uma cultura de E. coli AB1157, em fase estacionaria, foi incubada com nogueira e o crescimento da cultura foi avaliado por densidade optica a 600nm por 7 horas. Amostras de DNA plasmidial foram incubadas com SnCl2 na presenca ou ausencia de nogueira por 40 minutos, a eletroforese em agarose 0.8% foi realizada, o gel foi corado e as formas topologicas do plasmidio foram visualizadas. Amostras de sangue de ratos Wistar foram incubadas com extrato de nogueira e um ensaio de marcacao de constituintes sanguineos com tecnecio-99m (99mTc) foi realizado. Celulas sanguineas e plasma foram separadas. A radioatividade em cada fracao foi contada e a percentagem de radioatividade incorporada (%ATI) foi determinada. Os resultados apresentaram uma acao inibitoria do crescimento da cultura de E. coli AB1157, nenhuma acao protetora do extrato de nogueira em DNA plasmidial tratado com SnCl2. Alem disso, na nogueira tambem nao foi capaz de induzir modificacoes na mobilidade do DNA em gel de agarose, mas a nogueira foi capaz de diminuir a distribuicao de 99mTc no compartimento sanguineo celular. Concluindo, nosso resultado experimental sugere que no extrato de nogueira existem substâncias com um efeito no crescimento de cultura de E. coli, uma acao capaz de aumentar o efeito do SnCl2 no DNA plasmidial e tambem ser capaz de alterar a distribuicao de 99mTc no compartimento sanguineo celular provavelmente devido a propriedades redoxi.