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Radioactive implant migration in patients treated for localized prostate cancer with interstitial brachytherapy.

PURPOSE: In several of the initial patients undergoing brachytherapy at our institution radioactive implants were visible in the thorax on chest radiography. The clinical ramifications of this unanticipated finding were unclear. Thus, we investigated the incidence of brachytherapy seed migration to the chest and whether these seeds were associated with any clinical significance. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent ultrasound or computerized tomography guided brachytherapy of 103palladium seeds from March 1997 to March 1999. This list of patients on brachytherapy was then matched against the radiology computer system to determine those who had undergone chest X-ray after brachytherapy. When the radiology report was unclear regarding brachytherapy seeds, chest x-rays were reviewed by one of us (R. O.) to determine the presence and position of the seeds. RESULTS: Post-brachytherapy chest x-rays were available in 110 of the 183 patients. In 78 cases no brachytherapy seeds were identified. Radioactive implants were identified on chest radiography in 32 patients (29%), including 1 to 5 seeds in 20, 8, 1, 2 and 1, respectively. No patients complained of any change in pulmonary symptoms after brachytherapy. CONCLUSIONS: Radioactive implants migrated after brachytherapy for localized prostate cancer in 29% of the patients who underwent post-procedure radiography. There did not appear to be a pattern to the seed distribution. However, while the incidence was not negligible, no patient appeared to have any acute pulmonary symptoms. Therefore, while the migration of radioactive implants to the chest is a real phenomenon, it appears to have no adverse clinical consequences in the early post-procedure period.

Brachytherapy↗

Protein bound radioactivity in neuronal and glial fractions following intra-carotid 3H-leucine perfusion.

Brain proteins in one cerebral hemisphere were labeled by means of intracarotid perfusion with 3H-leucine by a 40 s pulse. Recirculating precursor contributed little to the protein bound radioactivity. This radioactivity reached a peak level 30 min after perfusion. Fractions enriched in neuronal perikarya and glial cells showed a similar time course of labeling, but the neuronal fraction demonstrated the highest level of protein bound radioactivity. Subcellular fractions from whole brain were studied by the same system. The highest protein bound radioactivity was observed in the nuclear and microsomal fractions. The brain entry of the precursor by means of a controlled intracarotid pulse of short duration offers particular advantages in short-term experiments since the systemic metabolism of the labeled precursor is largely avoided. The easily achieved high labeling of proteins facilitates assay of the radio-activities in different cellular and subcellular fractions and also allows analyses of relative turnover rates in electrophoretically separated proteins.

Animals↗

Prenatal diagnosis of alpha-thalassemia of Southeast Asian deletion with non-radioactive southern hybridization.

BACKGROUND: Alpha-thalassemia is a common hereditary disease in Taiwan. Affected patients always carry a heavy burden of morbidity and early death. Prenatal diagnosis has reduced the disease burden on families and the health care system. This study evaluated a new non-radioactive Southern blotting hybridization method for prenatal diagnosis of this disease. METHODS: Seventy two chorionic villi samples (CVS) and 30 amniocyte samples from 102 pregnancies of couples who were both heterozygous for alpha-thalassemia-1 of the Southeast Asian (SEA) type deletion were studied. A non-radioactive Southern blotting hybridization method using a dig-alkaline phosphate detection system was developed for use in this study. RESULTS: Non-radioactive Southern blotting hybridization data showed that 19 (26%) CVS and five (17%) amniotic fluid samples had 10 Kb and 4Kb fragments, indicating homozygosity of the alpha-thalassemia-1 SEA type deletion. DNA samples were extracted from most of the aborted tissue of the 24 fetuses with a diagnosis of homozygous for the alpha-thalassemia-1 SEA type deletion. Homozygosity for alpha-thalassemia-1 SEA type deletion was reconfirmed by Southern blotting hybridization in all of these samples. CONCLUSIONS: The non-radioactive Southern hybridization protocol used in this study allows efficient and accurate early prenatal diagnosis of alpha-thalassemia-1 SEA type deletion. It can be routinely used for testing couples who both carry the alpha-thalassemia-1 SEA type deletion.

Adolescent↗

The selective in vivo incorporation and metabolism of radioactive putrescine in the adult male rat.

Putrescine (1,4, diaminobutane), a known precursor of the polyamines, spermine, and spermidine, was studied as a possible vehicle for a radioisotope scan of the prostate and other tissues rich in polyamines. Male Sprague-Dawley rats received intravenous injections (2.3 muCi/100 gm) of 3H putrescine dihydrochloride (specific activity, 107 muCi/muM). One hour after injection the ventral prostate and pancreas showed uptake of radioactivity that was three and four times greater than that of the liver, respectively. The ratio of the amount of radioactivity in the ventral prostate compared with that of abdominal wall musculature was 8:1. The pancreas-to-muscle ratio was 10:1. At 1 hr the ventral prostate contained 0.6% (0.9%/gm wet wt) of the total injected radioactivity and the pancreas, 0.5% (1.2%/gm wet wt) of the injected dose. More than 90% of the radioactivity in the rat ventral prostate, 6 hr after intravenous injection of 14C-putrescine dihydrochloride, was found to be in the form of spermine and spermidine, thus confirming previous in vitro biosynthetic studies.

Abdominal Muscles↗

[A canine model of acute pulmonary thromboembolism induced by autologous radioactive blood clots].

OBJECTIVE: To establish a canine model of pulmonary thromboembolism (PTE) for evaluating the effects of thrombolytic therapy. METHODS: The preparations of radioactive blood clots in vitro were made from fresh whole blood (from 6 donors) mixed with (99m)Tc-SC. After eluting the clots with saline solution, the stability and evenness of (99m)Tc-SC in the clots were determined. Then a canine model of PTE induced by these clots was established and the rates of spontaneous lysis were measured by the regions of interest (ROI) technique and the in vitro method. RESULTS: (99m)Tc-SC was stable in the radioactive blood clots after elution, and the radioactivities in the thrombi were well-distributed. The rates of thrombolysis were (6.2 +/- 4.0)% as measured by ROI and (6.0 +/- 2.7)% by the in vitro method. CONCLUSIONS: (99m)Tc-SC is stable and well-distributed in blood clots. A canine model of PTE can be induced by autologous radioactive blood clots.

Animals↗

Treatment of toxic solitary thyroid nodules: surgery versus radioactive iodine.

BACKGROUND: Because of controversy about the correct treatment of toxic solitary thyroid nodules, we reviewed our experience. METHODS: We retrospectively studied 32 patients (24 women and 8 men) with solitary toxic thyroid nodules who were treated at our institution (1970 to 1985). RESULTS: Median values were as follows: age of patients at initial treatment, 67.6 years (range, 18.9 to 86.2 years); follow-up, 3.8 years; largest diameter of nodules, 3.3 cm (range, 1.5 to 6 cm); and 131I uptake at 24 hours, 31% (range, 7% to 54%). Nine patients had surgical treatment: subtotal thyroid lobectomy in six patients and subtotal thyroidectomy in three patients. Hypothyroidism developed in two of these nine patients (22%) 9 months after operation. No surgical complications occurred. No surgically treated patient had nodule recurrence or required re-treatment. Twenty-three patients were treated with radioactive iodine (median dose, 29.1 mCi; range, 19.7 to 100 mCi). Two of them were re-treated: one patient underwent thyroid lobectomy because of concern about the nodule, and one patient was re-treated with radioactive iodine because of persistent toxicity. Hypothyroidism was detected in eight of the 23 patients (35%) treated with radioactive iodine after treatment. Of the 16 patients treated with radioactive iodine with at least 1 year follow-up and no re-treatment, nine (56.3%) have had complete regression of the nodule. CONCLUSIONS: Surgical excision of solitary toxic thyroid nodules would appear to be the treatment of choice.

Adolescent↗

[Radioactivity of phosphorus implanted TiNi alloy].

Exposed to neutron flow, the phosphorus implanted TiNi alloy gets radioactive. This radioactive material is used in vascular stent for prevention and cure of restenosis. Phosphorus implantation is carried out in a plasma immerged ion implantation system, and the dose of phosphorus implantation is in the range of 2-10 x 10(17) cm-2. After ion implantation, the alloy is exposed to the slow neutron flow in a nuclear reactor, the dose of the slow neutron is 1.39-5.88 x 10(19) n/cm2. The radioactivity of the TiNi alloy was measured by liquid scintillation spectrometry and radio-chromic-film dosimetry. The result shows that whether the phosphorus is implanted or not, the TiNi alloy comes to be radioactive after exposure to neutron flow. Just after neutron irradiation, the radiation dose of phosphorus implanted TiNi alloy is about one hundred times higher than that of un-phosphorus implanted TiNi alloy. The radiation difference between phosphorus and un-phosphorus implanted alloy decreases as time elapses. Within three months after neutron irradiation, the average half-decay period of phosphorus implanted TiNi alloy is about 62 days. The radiation ray penetration of phosphorus implanted TiNi alloy is deeper than that of pure 32P; this is of benefit to making radiation uniformity between stent struts and reducing radiation grads beyond the edge of stent.

Alloys↗

Identification of transplanted pancreatic islet cells by radioactive dithizone-[131I]-histamine conjugate. Preliminary report.

BACKGROUND: The unique mechanism of dithizone action in the interior of the viable pancreatic islet suggests the possible development of a specific radiopharmaceutical that may have a potential clinical application in the diagnosis of the pancreatic organ allografts or islets rejection. The radiodiagnostic properties of the newly developed radioactive analogue of dithizone, i.e. Dithizone-[(131)I]-Histamine conjugate have been evaluated in the present study. METHODS: The four islet cells transplantation models were chosen for this purpose. The most important feature of the Dithizone-[(131)I]-Histamine conjugate is its possessed ability of zinc chelation. As was presented in the recent study, the conjugate stains pink-reddish the isolated pancreatic islets in vitro. Among the studied transplantation models, only the islets grafting under testis capsule enabled determination of the pancreatic islets in rats by radioactive Dithizone-[(131)I]-Histamine conjugate. The level of the radioactivity in the recipient testis (right) was almost two times higher compared to the controls (0.24 vs. 0.13% ID/g, respectively). CONCLUSIONS: These preliminary data demonstrate the ability of the developed radioactive analogue of dithizone for in vivo identification of transplanted pancreatic islets, and suggests a potential clinical application of the radiodithizone in the diagnosis of the pancreatic islet rejection.

Journal Article↗

[Experimental study of the thrombolytic effects in a canine model of pulmonary thromboembolism induced by autologous radioactive blood clots].

OBJECTIVE: To compare the thrombolytic effects of the two dosing regimes with urokinase (UK) in a canine model of pulmonary thromboembolism induced by radioactive blood clots. METHODS: Seventeen dogs were randomly assigned into three groups: the control group, the UK(2h) group (UK infused over 2 hours) and the UK(12h) group (UK given over 12 hours). The thrombolytic differences was investigated among the three groups. Thrombolysis was assessed by continuously counting over both lung fields with single photon emission computed tomography (SPECT) and calculated by regions of interest (ROI) technology and by counting radioactivity in the lung in vitro. The extent of thrombolysis was calculated as the difference between the radioactivity originally incorporated in the clot (decay-corrected) and the radioactivity in the lung in vitro. RESULTS: In three groups, the lysis rates measured by ROI technology were (6.2 +/- 4.0)%, (39.5 +/- 13.9)%, and (16.9 +/- 8.9)% respectively, and (6.0 +/- 2.7)%, (42.8 +/- 12.4)%, and (17.7 +/- 9.3)% by the method in vivo. The thrombolytic ratio of the UK(2h) group was significantly higher than that of the other two groups (P < 0.01), and there was no marked difference between the control group and the UK(12h) group. There was a thrombolytic peak in the UK(2h) group at the first four hours after infusion of agent. CONCLUSIONS: For the fresh thrombi, the UK(2h) regime is superior to the UK(12h) due to its higher thrombolytic ratio and prompt thrombolytic property. The model and methods are highly reliable.

Animals↗

Localization of the sentinel lymph node in breast cancer: prospective comparison of vital staining and radioactive tracing methods.

The aim of the study was to evaluate possible differences in accuracy between the radioactive tracing and vital staining method in the search for sentinel nodes in patients with breast cancer. From January 1999 to December 2000, 102 patients with T1 N0 breast carcinoma were recruited into the study for localization of sentinel nodes with vital blue dye staining and radioactive tracing and were then submitted to lumpectomy and axillary dissection. For the two methods, we estimated the percentage of sentinel nodes localized, the false-negative rate, the predictive negative and positive value and the accuracy. The vital blue dye staining method permitted localization of the sentinel node in 73% of patients with a false-negative rate of 8%, a predictive negative value of 92% and 92% accuracy. The radioactive tracing method permitted localization of the sentinel node in 97% cases with a false-negative rate of 0%, a predictive negative value of 100% and 100% accuracy (P<0.0005). The method that offers the better results is radioactive tracing. Currently, many authors use both techniques, since, in common practice, staining helps to identify the sentinel node with the probe.

Adult↗

Disappearance of radioactivity from perfusate of isolated rat liver after administration of different doses of tritiated DH-ergotoxine.

In ergot alkaloids a disproportion between the size of the peroral dose and the achieved area under the curve concentrations was described. This process can be explained by nonlinearity in the absorption, distribution or elimination of alkaloids. The aim of the present paper is to find whether elimination of tritiated DH-ergotoxine (3HDHE) in the liver is a linear, dose-independent process. Therefore on the model of the isolated rat liver disappearance of radioactivity in perfusate after the administration of two doses of 3HDHE, viz. 60 ng g-1 of the liver and 3030 ng g-1 of the liver, was investigated. The disappearance curves of radioactivity expressed as the percentage of the administered dose did not significantly differ between both groups. No significant changes between the groups were found either in the size of pharmacokinetic parameters, or in the portion of the administered radioactivity excreted in bile. Therefore the present authors think that disappearance of radioactivity in perfusate of the isolated liver after administration of 3HDHE is a linear process following first-order kinetics.

Animals↗

Distribution pattern of radioactive labelled lipiodol-UF following intralymphatic application for therapy.

Endolymphatic radiotherapy with 4 mCi32P tri-n-octylphosphate and 1 mCi 131 I triolein LIPIODOL UF has been performed in 75 patients suffering from malignant melanoma of the lower extremity. On the average, 13.3% of the radioactive substance remains in the syringes and connecting tubes. In most patients the radioactive material available for therapeutic irradiation is further reduced due to contamination of operation sheets and swabs (mean: 15.3%). There is, however, still sufficient radioactivity remaining for effective internal irradiation of the lymph nodes. The average radiation dose absorbed by the lymphatic tissue is 90.998 rad. The method is limited by the hazard of radiation damage to the lungs. Almost 80% of these patients had detectable concentrations of radioactivity in the lung fields. The average radiation dose was found to be 299 rad. So far radiation induced fibrosis has bot been observed in this series.

Humans↗

Pharmacokinetic study of radioactive antineoplaston A10 in rats and mice.

Fifteen Wistar rats were divided into three groups: low dose--150 mg/kg, medium dose--300 mg/kg and high dose--600 mg/kg. 3H-labelled antineoplaston A10 (3H-A10) was administered to the rats in all three groups. Blood was withdrawn from the tail vein, while urine and faeces were collected at different time intervals for the determination of radioactivity. The volume of distribution (Vd) was evaluated in the rats by intravenous dosage of 150 mg/kg of 3H-A10 dissolved in dimethyl sulfoxide. Thirty mice were divided into six groups and sacrificed at 1, 3, 6, 12, 24 and 36 h respectively after oral administration of H3-A10 for the study of radioactivity in various organs. It was observed that the concentration-time curves of A10 in the blood support a dicompartmental model of pharmacokinetics, and calculated values are very close to experimental values. The binding rate of A10 to plasma protein is 5.05% at 3 h after oral administration. Organ distribution studies indicated the highest accumulation of radioactivity in the bladder, followed by kidney, stomach, genitals and liver, whereas there was lower accumulation of radioactivity in the spleen, heart, brains and lungs.

Administration, Oral↗

Characterization of nonexchangeable radioactivity in L1210 cells incubated with [14C]thiotepa: labeling of phosphatidylethanolamine.

N,N',N''-Triethylenethiophosphoramide ([14C]thiotepa) accumulation by L1210 cells is a biphasic process. A very rapid initial phase is followed by a much slower second phase that reflects accumulation of radioactivity in a form that is not lost or exchanged when cells are resuspended and incubated in drug-free medium for up to 8 h. In this study we attempted to characterize this nonexchangeable radioactivity. Nuclei (10(7)) isolated from L1210 cells and incubated with [14C]thiotepa did not accumulate 14C during incubations of up to 5 h. Similarly, nuclei isolated from 10(7) L1210 cells that had been shown to accumulate nonexchangeable 14C after incubation with [14C]thiotepa did not show an increase in nuclear-associated 14C. Eighty to 85% of nonexchangeable 14C in L1210 cells incubated with [14C]thiotepa was soluble in ethanol or chloroform:methanol (2:1, v/v), and although most of this cell-associated nonexchangeable 14C was precipitated by trichloroacetic acid, subsequent treatment of that precipitate with methanol solubilized most of the 14C so that only 15 to 20% remained with the final precipitate. When chloroform:methanol-soluble nonexchangeable 14C was analyzed with thin-layer chromatography systems suitable for thiotepa or simple lipids, all radioactivity remained at the origin. In contrast, when analyzed with one- and two-dimensional thin-layer chromatographic systems suitable for complex lipids, all chloroform:methanol-soluble radioactivity was associated with a single lipid spot. This lipid cochromatographed with phosphatidylethanolamine, reacted with ninhydrin but not with 4-(p-nitrobenzyl)pyridine or the Dragendorff choline reagent, and was digested by phospholipases C and D, all of which lead to its identification as phosphatidylethanolamine. This extensive labeling of phosphatidylethanolamine in L1210 cells incubated with [14C]thiotepa can be explained by liberation of [14C]aziridine from [14C]thiotepa, hydrolysis of the [14C]aziridine to [14C]ethanolamine, and incorporation of that radiolabeled material into phosphatidylethanolamine via the normal cellular synthetic pathways for that lipid. This information implies that thiotepa serves, at least in part, as a prodrug for aziridine and has implications as to the mechanism of thiotepa-induced cytotoxicity in that aziridine is a monofunctional alkylating agent incapable of producing interstrand, intrastrand, or protein-DNA cross-links.

Animals↗

Elimination of radioactivity following administration of [15,16-3H]naltrexone to rats and guinea pigs.

The elimination of radioactivity after [15,16-3H]naltrexone administration was studied in rats and guinea pigs. An average of 42% of the dose was eliminated in urine and 55% in feces following administration of 1 mg/kg iv to each of three rats. Analysis of radioactivity in the excreta of one rat that received the same dose im yielded similar results. On the other hand, four guinea pigs that received 1 mg/kg iv excreted only 14% of the dose in feces and 84% in urine. Similar results were obtained following im administration to guinea pigs at 1 and 20 mg/kg doses. In guinea pig excreta, an average of 64% of the dose corresponded to naltrexone and conjugates, 19% to beta-naltrexol and conjugates, and 2% to alpha-naltrexol and conjugates. In urine, the radioactivity corresponding to alpha-naltrexol and naltrexone was present mainly in conjugated form, whereas apparent beta-naltrexol was mainly unconjugated. The radioactivity in feces corresponded principally to unconjugated naltrexone and beta-naltrexol.

Animals↗

[Distribution of radioactivity in subcellular fractions of genital tract tissue and skeletal muscles of guinea pig embryos after administration of 1 alpha,2 alpha-3H(n) testosterone in vitro].

The dynamics of radioactivity in subcellular fractions of the reproductive system and muscle has been studied in the guinea pig embryos from the 21st day of development till birth after the preincubation in a medium containing 1 alpha,2 alpha-3H(n) testosterone (T-3H). The total uptake of T-3H per mg tissue is higher in the reproductive system than in the muscle and attains the highest values during the period of differentiation of target organs by the male type (30-33 days). The nucleocytoplasmic ratio of radioactivity is shifted towards its increase in the nucleus with maximum on the 41st-45th days and by the moment of birth. Radioactivity in the microsomal fraction is higher than in the cytosol (soluble proteins). From the 27th day of development on, when the hormone uptake becomes selective, the radioactivity in the cytosol from the reproductive organs is higher than in the muscle tissue. The data obtained suggest the importance of processes in microsomes for differentiation and organogenesis of reproductive system.

Animals↗

Fractionation of radioactivity in the milk of goats administered 14C-aflatoxin B1.

A detailed fractionation of radioactivity in the milk of goats administered 14C-aflatoxin B1 at low doses was performed. The milk collected in the first 24 h following dosing contained radioactivity equivalent to 0.45-1.1% of the dose given. The radioactivity in each sample was partitioned into 4 fractions: ether, protein, dichloromethane, and water-alcohol. Over 80% of the radioactivity was detected in the dichloromethane fraction, of which over 95% was attributable to aflatoxin M1. No aflatoxin B1 or other known aflatoxin metabolites were detected in any fraction. The results indicate that the major metabolite of aflatoxin B1 in goat milk is aflatoxin M1 and that other metabolites, including conjugates, are of minor significance.

Aflatoxin B1↗

[Evaluation of the experience of the observer in the interpretation of myocardial scintillography with radioactive phosphates].

Two-hundred-and five myocardial scans with radioactive phosphates, performed in 185 patients interned at the Coronary Care Unit due to acute chest pain (147 myocardial infarcts: 58 coronary heart disease), were independently interpreted by six observers with different degrees of experience on the lectures of these kind of images (two nuclear physicians, two cardiologists, and two fellows of the Nuclear Medicine Unit). A series of six different grades of myocardial concentration of the radioactive phosphates, related to its osseous concentration were followed. Each observer reported the grade of concentration he found in each image. The fraction of myocardial infarcts and of coronary heart disease found by each observer in every grade of concentration were calculated. With these data, it was determined the optimal criterion level of each observer by which he attained the minor incidence of false negative and false positive results. Four observers found their optimal criterion level on 2F, where grades 0-2D are considered as negative, and grades 2F-4 are considered as positive. One observer found his optimal level at 2D (0-1: -; 2D-4: +) and other at 1 (0: -; 1-4: +. By using a decision matrix which relates results of the test with a binary outcome (normal, abnormal) to the actual diagnosis, also with a binary outcome (infarct, no infarct), the ratios for "sensitivity", "specificity" and "accuracy" were derived for each observer performing at his particular optimal criterion level. Our results suggests that the observer performance depends on his particular degree of experience in interpreting nuclear medical images and on his visual perception. It was concluded that it is necessary to periodically evaluate the individual optimal criterion level of the physicians in charge of the lectures of the myocardial images with radioactive phosphates, liable to shift with time in relation to the experience of the observer. The need of a more objective procedure to quantitate myocardial concentration of the radioactive phosphates is also implied.

Acute Disease↗