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[Bone-seeking radioactive substances in nuclear medicine].

The concept of bone affinity of a radioactive tracer is developed on theoretical grounds and is discussed on the basis of the various substances used in nuclear medical diagnosis of bone disease. On the basis of results on the uptake of very short lived nuclides and extremely large molecules, evidence is provided that the incorporation of the tracer in the apatite crystal is not a primary criterion of bone affinity since incorporation cannot take place on timelimiting grounds in the former case and on spatial grounds in the latter. The fixation on bone is therefore more likely the result of non-specific adsorption processes. The utility of a radioactive substance in practical application in nuclear medicine depends on the radioactive characteristics of the nuclide and on its behavior in the organism. In this context the quality of the scintigram is particularly dependent on the mode and rate of elimination of that fraction of the tracer that is not bound by the skeleton. The various mechanism which cause differences in the uptake of tracer by healthy and pathological bone tissue are discussed with special regard to the role of blood flow.

Barium↗

External radioactive reference markers in SPECT imaging of the dopamine system.

OBJECTIVE: External radioactive reference markers have been used to localize the canthomeatal (CM) line and correct for head rotation in perfusion brain SPECT. This ensures that regardless of the subject's head position or rotation under the SPECT camera, reconstructed transaxial slices are reoriented parallel to the CM line. This study was undertaken to demonstrate the value of external radioactive reference markers in dopamine SPECT imaging. METHODS: We compared visual and marker methods of reorienting the transaxial slices between dopamine and perfusion brain SPECT studies, respectively. These consisted of imaging normal controls and patients with Alzheimer's or Parkinson's disease using a triple-head camera. Intra- and interoperator variability of the visual and marker methods of reorientation was determined for both perfusion and dopamine studies. RESULTS: In both intra- and interoperator studies, the variability of image reorientation was significantly reduced (P = 0.0066 and 0.014, respectively) by using the marker method on dopamine images. The variability of reorientation using the marker method for a single operator with dopamine images was 3.0% coefficient of variation (CV), and for the interoperator study (5 different operators) this was 7.0% CV. CONCLUSION: This study demonstrated that SPECT imaging of the dopamine system with external radioactive reference markers significantly reduced the variability of determining the angle of reorientation. This resulted in a standardized and consistent method of reorienting transaxial slices, allowing comparison within and between subjects of pre- and postsynaptic dopamine SPECT studies.

Alzheimer Disease↗

Gastric emptying rate assessment based on the proportion of intra-abdominal radioactivity in the stomach.

UNLABELLED: Using scintigraphic techniques, the rate of gastric emptying is calculated by quantifying the absolute radioactivity within a gastric region of interest (intragastric method) with the time of meal completion considered 100% retention. However, this technique has significant limitations arising from subject movement and radionuclide gamma-ray attenuation, which may render curve fitting difficult, particularly in patients with gastroparesis. In an attempt to minimize these limitations, we have expressed the intragastric content as a percentage of the total abdominal radioactivity (abdominal method) and compared these two methods. METHODS: Forty-five subjects in a sitting position consumed a meal consisting of two fried eggs labeled with 99mTc, two slices of toast and 300 mL 5% glucose water (412 kcal). Data were acquired at a rate of one frame every 5 min from the left anterior oblique view. Using the two methods, the intragastric retention ratios at 30, 60, 90, 120 and 240 min and the 50% emptying time (T50) were obtained from both observation and calculation by power exponential fit. R2, representing goodness of fit of the nonlinear curve fitting, was calculated. RESULTS: There were no differences in the calculated values of T50 between the two methods. Quantitative estimates of T50 by extrapolation of a power exponential fit were feasible in 42 of the 45 subjects when the abdominal method was used, compared with only 29 of the 45 subjects when the intragastric method was used. In the 23 subjects with delayed emptying, quantitative estimates of T50 were feasible in 20 subjects when the abdominal method was used, compared with 7 subjects when the intragastric method was used. Using the abdominal method as opposed to the intragastric method also significantly improved R2. The difference between observed values and estimated values of T50 and intragastric retention ratios at 30, 90 and 120 min was smaller using the abdominal method. CONCLUSION: Scintigraphic measurement of gastric emptying calculated using the proportion of the abdominal radioactivity in the stomach offers substantial advantages over conventional methods, particularly in patients with gastroparesis.

Adult↗

Brachytherapy of a choroidal melanoma using radioactive gold grains: a long-term follow-up study.

PURPOSE: We used radioactive gold grains to treat a patient with choroidal malignant melanoma. Radioactive sources were placed into surgically constructed scleral pockets. The patient was followed up for six years after therapy to assess changes in the tumor, recurrence, and side effects. METHODS AND MATERIALS: A male patient presented with malignant melanoma arising from the choroidal membrane of the posterior pole of the left eyeball. We placed radioactive gold grains into surgically constructed scleral pockets adjacent to the tumor, arranged in a plane based on the Manchester's method. The patient was followed up for six years after treatment. RESULTS: The radiation dose was 120 Gy at the apex of the tumor, which slowly became smaller and completely disappeared at one year and 10 months after treatment. Tumor recurrence was not observed. Radiation dose at the ipsilateral lens was 280 cGy. Side effects associated with therapy were a decrease in visual acuity secondary to retinal degeneration and atrophy, but his vision was correctable with suitable glasses. In addition, the visual field of the left eye was also restricted. Mild cataracts also developed in the ipsilateral eye after treatment. CONCLUSION: Although this therapeutic method is technically difficult compared with other methods, it permits the tumor to be treated without loss of the eye. This may significantly improve the patient's quality of life.

Adult↗

Assessment of portosystemic shunt by summation of radioactivity during 201thallium chloride portal scintigraphy in patients with chronic liver disease.

BACKGROUND/AIMS: Portal scintigraphy is a useful non-invasive method for the determination of portosystemic shunts in patients with liver cirrhosis. Several procedures have been reported for its execution in clinical practice but most of them failed to show sufficient sensitivity for the diagnosis of portosystemic shunt. In the present study, we evaluated whether summation of radioisotope counts obtained during intrarectal or intraduodenal administration of 201thalium chloride is useful for increasing the diagnostic yield of porto-systemic shunts in patients with chronic liver disease. METHODOLOGY: Seven patients with chronic viral hepatitis and 8 with liver cirrhosis secondary to viral hepatitis were enrolled in this study. Following the conventional protocol, 201thalium chloride was administered per rectum and the 60-second-heart-to-liver uptake (conv-H/L-R) ratio was calculated after 20 min. Continuous measurement of the radioactivity signals during 20 min were also done and the summated heart-to-liver uptake (sum-H/L-R) ratio from the total radioactivity count were calculated. Measurement of the conventional heart-to-liver uptake (conv-H/L-D) ratio and the summated (sum-H/L-D) ratio were also done as described above after the intraduodenal administration of 201thalium chloride by endoscopy. RESULTS: All ratios (conv-H/L-R, conv-H/L-D, sum-H/D-R, sum-H/L-D) were significantly higher in patients with liver cirrhosis than in those with chronic hepatitis. Among all heart/liver ratios, only the sum-H/L-R ratio was significantly different between patients with and without esophageal varices. Serum hyaluronate level and other liver function tests were found to be significantly correlated with all heart-to-liver ratios, but they were more strongly correlated with the sum-H/D-R and sum-H/L-D ratios than with the conv-H/L-R and conv-H/L-D ratios. CONCLUSIONS: The results of this study showed that the heart-to-liver ratio calculated by summation of radioactivity is better than the conventional method for the diagnosis of portosystemic shunt in patients with chronic liver disease.

Adult↗

Protection of the public in situations of prolonged radiation exposure. The application of the Commission's system of radiological protection to controllable radiation exposure due to natural sources and long-lived radioactive residues.

This report provides guidance on the application of the ICRP system of radiological protection to prolonged exposure situations affecting members of the public. It addresses the general application of the Commission's system to the control of prolonged exposures resulting from practices and to the undertaking of interventions in prolonged exposure situations. Additionally, it provides recommendations on generic reference levels for such interventions. The report also considers some specific situations and discusses a number of issues that have been of concern, namely: natural radiation sources that may give rise to high doses; the restoration and rehabilitation of sites where human activities involving radioactive substances have been carried out; the return to 'normality' following an accident that has released radioactive substances to the environment; and the global marketing of commodities for public consumption that contain radioactive substances. Annexes provide some examples of prolonged exposure situations and discuss the radiological protection quantities, radiation-induced health effects and aspects of the Commission's system of radiological protection relevant to prolonged exposure. Quantitative recommendations for prolonged exposures are provided in the report. They must be interpreted with extreme caution; Chapters 4 and 5 stress the upper bound nature of the following values: Generic reference levels for intervention, in terms of existing total annual doses, are given as < approximately 100 mSv, above which intervention is almost always justifiable (situations for which the annual dose threshold for deterministic effects in relevant organs is exceeded will almost always require intervention), and < approximately 10 mSv, below which intervention is not likely to be justifiable (and above which it may be necessary). Intervention exemption levels for commodities, especially building materials, are expressed as an additional annual dose of approximately 1 mSv. The dose limit for exposures of the public from practices is expressed as aggregated (prolonged and transitory) additional annual doses from all relevant practices of 1 mSv. Dose constraints for sources within practices are expressed as an additional annual dose lower than 1 mSv (e.g. of approximately 0.3 mSv), which could be approximately 0.1 mSv for the prolonged exposure component. An exemption level for practices is expressed as an additional annual dose of approximately 0.01 mSv.

Cosmic Radiation↗

Non-radioactive Southern hybridization for early diagnosis of alpha-thalassemia with southeast Asian-type deletion in Taiwan.

Alpha-thalassemia has been estimated to account for over 60% of hydrops fetalis cases in Taiwan. The most common genotypic lesion found in alpha-thalassemia-1 cases in Taiwan is deletion of a large segment of the alpha-globin gene cluster, termed the Southeast Asian-type deletion (-SEA/; further referred to as SEA-type deletion). Seven chorionic villus samples (CVS) from pregnancies of couples both heterozygous for SEA-type deletion were studied. Non-radioactive Southern-blot hybridization using the dig-alkaline phosphatase detection system was developed to fulfill this purpose. The results were compared with corresponding polymerase chain reaction (PCR) data to elucidate the effectiveness of these two protocols in the diagnosis of the SEA-type deletion. The data showed that of the seven CVS, three demonstrated a distinctive band pattern, indicating their homozygous status of SEA-type deletion, whereas two showed heterozygous patterns, and the other two were free of the deletion. Homozygosity of the deletion was confirmed by Southern-blot hybridization performed on DNA samples extracted from the abortus tissue. However, two of the three cases with SEA-type deletion showed heterozygous PCR results. Maternal cell contamination could be responsible for the artifacts in the PCR results, but the influence due to the contamination is minimal in non-radioactive Southern-blot hybridization. We concluded that PCR is suitable for screening of carrier adults with SEA-type deletion, and non-radioactive Southern hybridization is ideal for early prenatal diagnosis of the SEA-type deletion.

Asia, Southeastern↗

Plasma disappearance of radioactivity after intravenous injection of labeled bile acids in man.

The kinetics of disappearance of radioactivity from plasma after intravenous injection of radiolabeled bile acids was characterized in healthy subjects. Cholic and chenodeoxycholic acids and their N-glycine and N-taurine conjugates were studied along with the secondary bile acid, deoxycholic acid, and a synthetic conjugated bile acid, dehydrocholyltaurine. Disappearance of each primary bile acid was rapid and could be described by a biexponential curve (t 1/2 the first component, 1.7 to 3 min; second component, 7 to 16 min). Cholyglycine and cholyltaurine had identical disappearance rates which were significantly faster than the disappearance rates of chenodeoxycholylglycine and chenodeoxycholyltaurine, which were also identical. Radioactivity of a conjugated bile acid disappeared more rapidly than that of its unconjugated form, but all of these differences, although consistent, were small. Deoxycholic acid radioactivity disappeared slightly more slowly than that of the primary bile acids. In vitro, dihydroxy bile acids were bound by serum proteins more completely (96 to 98%) than trihydroxy bile acids (83 to 91%), whether free or conjugated, and binding was unrelated to bile acid concentration. Thus, plasma disappearance rates were related to the degree of protein binding to some degree in that those bile acids which were more tightly bound had the longer t 1/2 values. However, dehydrocholyltaurine showed little protein binding (42%), yet had the slowest disappearance rates; t 1/2 values averaged 4 and 36 min for the two components of the disappearance curve. The results suggest that the residence time of any bile acid in blood is extremely short, and that measurable concentrations of serum bile acids persist only because of continuous intestinal absorption. It is speculated that the reported difference between the pattern of fasting state serum bile acids and biliary bile acids is explained by differences in intestinal absorption and hepatic uptake of individual bile acids.

Adult↗

The incorporation of orally fed radioactive gamma-linolenic acid and linoleic acid into the liver and brain lipids of suckling rats.

The incorporation of radioactivity from orally administered gamma-linolenic acid-1--14C and linoleic acid--3H into the liver, plasma, and brain lipids of suckling rats was studied. Significantly more radioactivity from the former compound was incorporated into the liver and brain lipids 22 hr after dosing. The distribution of the radioactivity in the fatty acids of the liver and brain lipids was different for each isotope. Most of the -3H was still associated with linoeic acid, whereas most of the -14C was in the 20:3 and 20:4omega6 fractions. These results suggest that the desaturation of linoleic to gamma-linolenic acid in vivo is a rate-limiting step in the conversion of linoleic to arachidonic acid.

Administration, Oral↗

Effect of vascular radioactivity on regional values of cerebral blood flow: evaluation of methods for H(2)(15)O PET to distinguish cerebral perfusion from blood volume.

UNLABELLED: To evaluate the appropriate model for calculating regional cerebral blood flow (rCBF) with PET and H(2)(15)O, the values obtained from 1- and 2-compartment analyses were compared. METHODS: Dynamic PET scans were performed on 12 healthy volunteers after injection of H(2)(15)O in 2 conditions of baseline and visual stimulation. Calculation of rCBF was performed using the 2-weighted integral (WI) and autoradiographic methods for the 1-compartment analysis, and the 3-WI method was followed for the 2-compartment analysis. Arterial blood radioactivity was counted continuously and corrected for delay and dispersion. The rCBF images were transformed into the Talairach space and analyzed by statistical parametric mapping to identify regional differences in the 2 methods. The values obtained from regions of interest also were compared. RESULTS: Although the difference in global CBF between the 2 models was not significant, rCBF values in the large arteries and neighbor areas were significantly greater in the 2-WI method than in the 3-WI method. However, regional differences in the activation studies were not affected when the 2 methods were compared. The images of cerebral arterial blood volume (V(0)) obtained by the 3-WI method showed a significant increase in V(0) in the visual cortex during visual stimulation. CONCLUSION: These results suggest that the rCBF values in the 1-compartment analysis were affected by radioactivity in the vessels. The 3-WI method could provide rCBF values that are less influenced by vascular radioactivity and also show differences in V(0) in PET activation studies.

Adult↗

[Application of radioactive substances in nuclear medicine research: current trends and radiation exposure of study subjects].

AIM: Analysis of the application of radioactive substances in research in the field of nuclear medicine in human beings and of the resulting radiation exposure to study subjects. METHODS: Assessment of applications for approval submitted in accordance with Paragraph 41 of the Radiation Protection Ordinance, evaluated by the Federal Office for Radiation Protection together with the Federal Institute for Pharmaceuticals and Medical Products, within the period from 1997 to 1999. RESULTS: The focus of the studies on the diagnostic application of radioactive substances in medicine evaluated has, since 1998, shifted from oncological to neurological and psychological aspects, while, at the same time, the number of PET studies increased constantly. The proportion of healthy study subjects included in the diagnostic studies increased from 7 to 22%. The number of therapeutic applications of radioactive substances has, since 1997, undergone a three-fold increase, and in the process of this, the focus of attention lay within the area of radioimmuno-therapy and endovascular brachytherapy. The effective dose was, among up to 49% of the investigated healthy study subjects higher than 5 mSv, and among up to 6% of these subjects was at levels of over 20 mSv. Up to 22% of the patients received, within the scope of diagnostic studies, an effective dose of between 20 and 50 mSv. An exceeding of the 50 mSv limit occurred among up to 3% of the patients. CONCLUSIONS: In spite of the increasing numbers of PET applications, conventional nuclear medicine has maintained its importance in the field of medical research. Further developments in the areas of radiochemistry and molecular biology led to an increase in the importance of radio-immuno therapy. The evaluation of new radiopharmaceuticals and the extension of basic biomedical research, resulted in an increase in the proportion of healthy study subjects included in the studies. The radiation exposure among subjects resulting directly from the studies showed, for the period of evaluation, an overall trend towards reduction.

Humans↗

Alteration of L cell growth by antibody-stimulated incorporation of radioactive nucleosides.

Radioactive nucleoside incorporation into mouse L cells was stimulated by exposure of the cells to rabbit anti-L cell antibody. Use of nucleosides of high specific radioactivity permitted a selective reduction of replication of antibody-treated cells as compared to control cells. The mechanism most likely involves radioactive damage of nuclear contents and DNA.

Animals↗

Isoelectric focusing of pure rat pancreatic juice in polyacrylamide gel : possibility of concomitant estimation of radioactivity incorporated into single identified protein constituents.

A method is described for the isoelectric focusing of rat pancreatic juice on columns of polyacrylamide gel containing urea. Twenty-six bands were separated, and 6 were identified. Application of this method of separation to in vivo radioactively labelled pancreatic juice resulted in bands which could be counted with precision. This procedure allowed also the expression of radioactivity of one constituent relative to any single band, or relative to total radioactivity, concomitantly.

Acrylamides↗

Internalisation and retention of EGF-dextran associated radioactivity in transfected Chinese hamster ovary cells expressing the human EGF-receptor.

Chinese hamster ovary (CHO) cells transfected with the wild-type gene for the human epidermal growth factor-receptor (EGFR) and expressing the receptor in their cell membrane are, together with the receptor negative parent CHO cells, an interesting model system for experimental EGFR-targeting tumour therapy. Comparisons of effects on nearly identical cells with and without receptors can be made. The main purpose of this work was to compare the internalisation and retention of the radioactivity delivered as 125I-EGF or 125I-EGF-dextran in transfected cells (called CHO-EGFR), and human glioma cells U-343 which naturally express wild-type EGFR. We found that radioactivity delivered as 125I-EGF-dextran was retained intracellularly by both cell types to a higher degree than radioactivity delivered as 125I-EGF. Prolonging the cellular exposure time for 125I-EGF-dextran considerably increased postincubation intracellular retention in both cell types. No major differences between the two EGFR expressing cell lines were found and, based on the results in this work, CHO-EGFR cells seem an adequate model for experiments with agents targeting the EGF-receptor.

Animals↗

Radioactive iodine in the treatment of Graves' disease.

OBJECTIVES: This study was performed to evaluate the efficacy of radioactive iodine 131I therapy of Graves' hyperthyroidism at Sultan Qaboos University Hospital, Oman and to determine the optimal dose of 131I needed to achieve the euthyroid or hypothyroid status. METHODS: The medical records of 366 patients with Graves hyperthyroidism who received a single dose of 131I at Sultan Qaboos University Hospital, Oman between 1991 and 1999 were reviewed. The diagnosis was based on clinical, biochemical grounds and 99mTc thyroid scintigraphy. The patients were followed up for a minimum period of 12 months. For the analysis, the patients were divided into 6 groups according to the 131I dose administered: Dose one (350-399), dose 2 (400-449), dose 3 (450-499), dose 4 (500-549), dose 5 (550-599) and dose 6 (> or = 600) MBq. RESULTS: Fifty-eight percent of all the patients were hypothyroid after 3 months. Three hundred and twenty two patients (88%) were treated by a single dose of 131I in 12 months (85.5% hypothyroid and 2.5% euthyroid). Forty-one patients (11.2%) required a 2nd 131I dose and only 3 patients required 3 doses of 131I. The best cure rate (93%) was observed in group dose 5 (574.0 +/- 16.4 MBq) which however, was not significantly different from other dosage levels. The female to male ratio was 2:1 and the cure rates were not gender or age related. CONCLUSION: Treatment of Graves' hyperthyroidism from a single 131I dose is our aim, rather than avoidance of hypothyroidism. Our results indicate that cure rates are higher with larger doses of 131I except in group dose 6 (special category of patients). In the future, fixed doses would be adopted in our radioactive iodine treatment practice guidelines. As the majority of our patients were hypothyroid at 3 months regular monthly follow-up is essential. Whenever appropriate, physicians are encouraged to consider early referral of Graves' hyperthyroidism patients for radioactive iodine treatment as it is cheap, effective, easy to administer and free from serious side effects.

Adult↗

Radioactive cesium in dirt accumulations on the roof of buildings.

The concentrations of 137Cs and 134Cs in dirt deposits on the roofs of buildings are much higher than those in the surface of soil at ground level. Thus dirt on roofs concentrates radioactive cesium in fall-outs. The 137Cs concentration in dirt deposits on the roofs of older buildings is not consistently higher than that on the roofs of new ones, but the 137Cs/134Cs ratio is higher in deposits on older buildings constructed before the first half of the 1970s, and decreases exponentially with decrease in age of the buildings gradually reaching 1.9 +/- 0.2, the value in the air-borne dust at the time of the Chernobyl accident. From this relationship, the contribution of Chernobyl radioactivity to accumulated 137Cs was calculated as 32% on buildings constructed in 1962. The radioactive cesium concentrations in dirt deposits in gutters of private houses and on the roofs of university buildings in Japan were also determined.

Air Pollutants↗

[Non-radioactive PCR southern method for analysis of CTG repeat in myotonic dystrophy].

Myotonic dystrophy (MyD) is a hereditary neuromuscular disorder of an autosomal dominant trait. MyD is caused by an expansion of unstable CTG trinucleotide repeat in the 3' untranslated region of mRNA coding myotonin protein kinase (MT-PK). We analyzed CTG repeat expansion in 10 patients with congenital MyD and their relatives using the non-radioactive PCR Southern method. The region containing the CTG repeat was amplified by PCR using specific primers. The PCR products were electrophoresed on a 1% agarose gel and transferred to a nylon membrane. The CTG repeat expansion was shown using a fluorescein-labelled (CTG) 10 probe. To estimate the number of CTG repeats, we compared the smears obtained on Southern blotting with a picture of PCR products and a DNA size marker (100 bp). We compared our results of radioactive Southern blotting for genomic DNA digested by Eco RI or Bgl I and for PCR products. In congenital MyD patients, heterogeneous smears (3.89-10.22 kb:about 1252-3362 CTG repeat) were observed, whereas in the adult type MyD had heterogeneous smears (0.92-1.82 kb:about 262-562 CTG repeat). In asymptomatic MyD patients, there were heterogeneous smears (0.35-1.16 kb:about 72-342 CTG repeat). These results demonstrated anticipation. We conclude that the non-radioactive PCR Southern method is useful and convenient for the DNA diagnosis of MyD.

Adult↗

Determining the site of brain tumors; the use of radioactive iodine and phosphorus.

By tests using radioactive iodine combined with diiodofluorescein, the site of tumors was correctly determined in 61 per cent of 39 cases of tumors of the cerebral hemispheres. In 19 cases where the focal radioactivity was increased 24 per cent or more over that of the surrounding area, there were no errors in localization. Fifteen patients with expanding intracranial lesions were tested at operation with radioactive phosphorus and 14 lesions were correctly localized. This procedure in which the needle probe was used was found of great value in rapidly locating and outlining the area of involvement.

Brain↗