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PubMed2000

Diagnostic value of routine radioisotope bone scanning in a series of 63 patients with pulmonary sarcoidosis.

BACKGROUND AND AIM: Routine use of diagnostic radioisotope bone scanning in patients with sarcoidosis has not previously been evaluated. The aim of this study was to assess whether routine radioisotope bone scanning might be of value in the detection of osseous lesions in sarcoidosis. METHODS: 63 consecutive Caucasian patients (32 men) with a median age of 39 years (range 17-66) and biopsy proven pulmonary sarcoidosis were included. None had symptoms suggesting osseous sarcoidosis. Extrathoracic, non-osseous sarcoidosis was present in 24 patients; 13 patients were on oral steroids. Radioisotope bone scanning was performed with a gammacamera after intravenous injection of 99mTechnetium-methylenediphosphonate. An abnormal bone scan was followed by a radiograph of the region of interest. RESULTS: 39 patients (61.9%) had normal bone scans. Minor bone scan abnormalities were found in 24 patients (38.1%). Of these, 11 patients had bone foci (8 in the vertebral spine, 9 in the ribs, 1 in a finger). Radiographically only one of these 11 patients had a bony lesion being typical of sarcoidosis, located in the second finger. 17 patients had joint foci. Radiographs of the joints showed sequelae after a fracture in 1 patient, and degenerative osteoarthritis in 1 patient. There was no difference between clinical and paraclinical variables in patients with normal and abnormal bone scans. CONCLUSIONS: There appears to be no indication for routine radioisotope bone scanning in patients with sarcoidosis. Scanning should be restricted to patients with clinical suspicion of osseous sarcoidosis.

Adult↗

PubMed1989

[Diagnosis of gastroesophageal reflux by radioisotopic techniques].

We evaluated 148 patients (mean age 45 years) with clinically evident gastroesophageal reflux. A radioisotopic test with 99mTc sulphur-colloid was performed in all; endoscopy in 146, biopsy in 24, acid reflux test and manometric evaluation in 141 and radiologic studies in 85. Sensitivity of the different techniques was: radioisotopes 92%, radiology 87%, acid reflux test 84%; endoscopy 63% and manometric studies 61%. Severity of reflux and esophagitis was adequately predicted from radioisotopic evaluation. We conclude that this radioisotopic test is highly reliable for the diagnosis of gastroesophageal reflux.

Adolescent↗

PubMed2006

Efficacy of 99mTc pertechnetate and 131I radioisotope therapy in sodium/iodide symporter (NIS)-expressing neuroendocrine tumors in vivo.

PURPOSE: There is growing interest in the human sodium/iodide symporter (NIS) gene both as a molecular imaging reporter gene and as a therapeutic gene. Here, we show the feasibility of radioisotope therapy of neuroendocrine tumors. As a separate application of NIS gene transfer, we image NIS-expressing tumors with pinhole SPECT in living subjects. METHODS: Biodistribution studies and in vivo therapy experiments were performed in nude mice carrying stably NIS-expressing neuroendocrine tumor xenografts following i.v. injection of (131)I and (99m)Tc pertechnetate. To show the usefulness of NIS as an imaging reporter gene, (99m)Tc pertechnetate uptake was imaged in vivo using a clinical gamma camera in combination with a custom-made single pinhole collimator, followed by SPECT/small animal MRI data coregistration. RESULTS: NIS-expressing neuroendocrine tumors strongly accumulated (131)I and (99m)Tc pertechnetate, as did thyroid, stomach, and salivary gland. The volume of NIS-expressing neuroendocrine tumors decreased significantly after therapeutic administration of (131)I or (99m)Tc pertechnetate, whereas control tumors continued to grow. NIS-mediated uptake of (99m)Tc pertechnetate could be imaged in vivo at high resolution with a clinical gamma camera equipped with a custom-made single pinhole collimator. High-resolution functional and morphologic information could be combined in a single three-dimensional data set by coregistration of SPECT and small animal MRI data. Lastly, we demonstrated a therapeutic effect of (99m)Tc pertechnetate on NIS-expressing neuroendocrine tumors in cell culture and, for the first time, in vivo, thought to be due to emitted Auger and conversion electrons. CONCLUSIONS: NIS-expressing neuroendocrine tumors efficiently concentrate radioisotopes, allowing for in vivo high-resolution small animal SPECT imaging as well as rendering possible successful radioisotope therapy of neuroendocrine tumors.

Animals↗

PubMed2005

Radioisotopes for the palliation of metastatic bone cancer: a systematic review.

Strontium-89 and samarium-153 are radioisotopes that are approved in the USA and Europe for the palliation of pain from metastatic bone cancer, whereas rhenium-186 and rhenium-188 are investigational. Radioisotopes are effective in providing pain relief with response rates of between 40% and 95%. Pain relief starts 1-4 weeks after the initiation of treatment, continues for up to 18 months, and is associated with a reduction in analgesic use in many patients. Thrombocytopenia and neutropenia are the most common toxic effects, but they are generally mild and reversible. Repeat doses are effective in providing pain relief in many patients. The effectiveness of radioisotopes can be greater when they are combined with chemotherapeutic agents such as cisplatin. Some studies with 89Sr and 153Sm indicate a reduction of hot spots on bone scans in up to 70% of patients, and suggest a possible tumoricidal action. Further studies are needed to address the questions of which isotope to use, what dose and schedule to use, and which patients will respond.

Bone Neoplasms↗

PubMed1997

Induction of the suicide HSV-TK gene by activation of the Egr-1 promoter with radioisotopes.

In investigating new methods for the treatment of pancreatic cancer, we have explored the possibility of using a combination of radiation and gene therapies. We demonstrate herein that the early growth response gene 1 promoter (Egr-1) is sufficient to confer selective expression of the luciferase gene (Luc) in a human pancreatic tumor cell line (AsPc-1) when exposed to ionizing radiation. The Egr-1 promoter directed the radioinducible expression of luciferase, and yielded higher levels of Luc activity than that in nonirradiated lines. The radioisotopes Tc-99m, I-131, and Ga-67-citrate were selected as Egr-1 activators for their potential to accumulate in tumors. We studied Ga-67-citrate, a radioisotope employed in tumor scintigraphy, for its suitability for selective gene induction. The plasmid vector pEgr-1-Luc was transfected into AsPc-1 cells and then exposed to radioisotopes. Luciferase activity increased by 100-300 times over control. We also inserted the herpes thymidine kinase gene (TK) downstream of Egr-1 and transfected this construct into AsPc-1 cells. Ga-67-citrate and ganciclovir were added to the cells and cell survival was assessed by MTT assay. The growth of AsPc-1 cells transfected with the pEgr-TK construct was suppressed 2 days after exposure of the cells to Ga-67-citrate. The results indicate that Ga-67-citrate may be useful in combining radiation and gene therapies.

DNA-Binding Proteins↗

PubMed1990

The effects of radioisotopes used in nuclear medicine on diagnostic radioimmunoassay testing. Is there any significant interference?

The administration of radioisotopes for diagnostic nuclear medicine scans and therapeutic procedures is quite prevalent today. A period of interference with the counting of a radioimmunoassay [RIA] test may occur with the serum of a patient receiving an in vivo radionuclide that decays by gamma emission. Because the logistics of precounting all specimens may be cumbersome and prohibitive, it is important to determine the degree of this interference. In this study, the authors evaluate the potential interference of the most commonly used radioisotopes with RIA studies. For two months (March and August 1988) 10,650 patient serum specimens were counted for significant background gamma radiation before RIA testing. Forty-three patients, on whom 105 RIA tests were performed, were identified as having preassay gamma radiation in their serum. With the use of selective energy windows for each different interfering radionuclide, proportional determinations were made as to the amount of interfering gamma radiation spilling into the iodine 125 test marker window. It was shown that initial whole serum pretest gamma counts as high as 111,000 counts/minute did not significantly affect the results of the RIA. Because of the meticulous washing and decanting procedures required in modern RIA and the monoclonal nature of most antibodies used currently, it appears the degree of nonspecific binding of this potentially interfering radiation is minuscule. The energy level of cobalt 57, however, and many of the other commonly used radioisotopes, overlaps so closely that it is difficult to window for this interference. It is possible, therefore, that this distinction cannot be made and folate and vitamin B12 test systems using cobalt 57 markers may have to be routinely prescreened. The authors conclude that the requirement for prescreening of all RIA test samples for interfering gamma radiation is unnecessary (1987 CAP Commission on Laboratory Accreditation Inspection Checklist, Section VII, Question 07.0290).

Diagnostic Techniques, Radioisotope↗

PubMed1983

Use of a gamma- or hard beta-emitting radioisotope to assess milk intake in suckling mouse pups.

A radioisotopic method to assess milk intake during suckling in mice is described. The method is based on the transfer of a gamma- or hard beta-emitting radioisotope from the lactating mother to the litter. The radioactivity of individual pups is determined at intervals by whole-body counting. The transfer of 22Na, 32P as orthophosphate, 51Cr as chromate, and 125I as iodide was examined; 125I showed particularly suitable characteristics. The procedure proved to be simple, accurate and reproducible for the comparison of mild consumption between pups within a litter and between litters. The procedure was suitable for studies using a foster mother.

Animal Population Groups↗

PubMed2003

Surface-modified poly(lactide-co-glycolide) nanospheres for targeted bone imaging with enhanced labeling and delivery of radioisotope.

Surface-modified nanospheres can be utilized for targeting drugs and diagnostic agents to the bone and bone marrow while extending their circulation time in the blood stream. The surface modification of poly(lactide-co-glycolide) (PLGA) nanospheres by radioisotope carrying poly(ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) triblock copolymers (Poloxamer 407) has been assessed by in vitro characterization and in vivo biodistribution studies after intravenous administration of the nanospheres to the mouse. A hydroxyphenylpropionic acid, a ligand for (125)I and (131)I labeling, was conjugated to the hydroxyl group of the Poloxamer 407 by using dicyclohexyl carbodiimide. The ligand-conjugated Poloxamer 407 was adsorbed onto the surface of PLGA nanospheres. Surface coating was confirmed by measuring both size distribution and the surface charge of the nanospheres. Besides, (125)I-labeling efficiency, radiolabeling stability, whole body imaging, and biodistribution of the radioisotope-labeled nanospheres were examined. Ligand-labeled, surface-modified PLGA nanospheres were in 100-nm size ranges, which may be adequate for long-circulation and further bone imaging. (125)I-labeling efficiency was >90% and was more stable at human serum for 24 h. A noticeable decrease in liver or spleen uptake was obtained by the surface-modified nanospheres. (125)I-labeled nanospheres showed higher blood maintenance and bone uptake compared with stannous colloid with the same size distribution. Therefore, a fully biodegradable, radioisotope-carrying, surface-modified nanosphere system has been developed as a promising tool for targeting bone and bone marrows.

Animals↗

PubMed2005

A comparison of PET imaging characteristics of various copper radioisotopes.

PURPOSE: PET radiotracers which incorporate longer-lived radionuclides enable biological processes to be studied over many hours, at centres remote from a cyclotron. This paper examines the radioisotope characteristics, imaging performance, radiation dosimetry and production modes of the four copper radioisotopes, ( 60)Cu,( 61)Cu,( 62)Cu and( 64)Cu, to assess their merits for different PET imaging applications. METHODS: Spatial resolution, sensitivity, scatter fraction and noise-equivalent count rate (NEC) are predicted for( 60)Cu,( 61)Cu,( 62)Cu and( 64)Cu using a model incorporating radionuclide decay properties and scanner parameters for the GE Advance scanner. Dosimetry for( 60)Cu,( 61)Cu and( 64)Cu is performed using the MIRD model and published biodistribution data for copper(II) pyruvaldehyde bis(N(4)-methyl)thiosemicarbazone (Cu-PTSM). RESULTS: (60)Cu and( 62)Cu are characterised by shorter half-lives and higher sensitivity and NEC, making them more suitable for studying the faster kinetics of small molecules, such as Cu-PTSM.( 61)Cu and( 64)Cu have longer half-lives, enabling studies of the slower kinetics of cells and peptides and prolonged imaging to compensate for lower sensitivity, together with better spatial resolution, which partially compensates for loss of image contrast.( 61)Cu-PTSM and( 64)Cu-PTSM are associated with radiation doses similar to [(18)F]-fluorodeoxyglucose, whilst the doses for( 60)Cu-PTSM and( 62)Cu-PTSM are lower and more comparable with H(2) (15)O. CONCLUSION: The physical and radiochemical characteristics of the four copper isotopes make each more suited to some imaging tasks than others. The results presented here assist in selecting the preferred radioisotope for a given imaging application, and illustrate a strategy which can be extended to the majority of novel PET tracers.

Computer Simulation↗

PubMed2005

Sympathetic nerve function--assessment by radioisotope dilution analysis.

Radioisotope dilution measurements of norepinephrine spillover (rate of entry of the transmitter into plasma) provide more accurate assessments of sympathoneural transmitter release than allowed by measurements of plasma catecholamine concentrations alone. Measurements of total body norepinephrine spillover, as an index of global sympathetic outflow, allow effects on plasma clearance to be distinguished from effects on release of catecholamines into plasma, while spillovers from specific tissues enable examination of regionalized sympathetic responses. However, spillovers of norepinephrine represent only a fraction of the transmitter that escapes neuronal and extraneuronal uptake after release by nerves. Numerous factors may influence this fraction and measures spillovers independently of transmitter release by nerves. Modified radioisotope dilution methods for assessment of rate processes operating within and between intracellular and extracellular compartments have further improved our understanding of the relationships of norepinephrine release, uptake, spillover, turnover, and metabolism. This article reviews the breadth of information about sympathetic nerve function attainable using catecholamine radioisotope dilution analyses against a backdrop of the relative advantages and methodological limitations associated with the methodology.

Animals↗

PubMed1992

Quantification and comparison of chloramphenicol acetyltransferase activity in transformed plant protoplasts using high-performance liquid chromatography- and radioisotope-based assays.

Rice and petunia leaf and cell suspension protoplasts were transformed by electroporation in the presence of pDW2. This plasmid contains a chloramphenicol acetyltransferase (CAT) coding region under the control of a promoter constructed from sequences of the cauliflower mosaic virus genome. We have compared two different approaches to measuring CAT activity in this system, namely high-performance liquid chromatography (HPLC) and a radioisotope-based method. Our results show that both techniques have a similar detection limit of 10 mU CAT and (with an activity greater than 10 mU CAT) the standard error for measuring known amounts of CAT activity was less than +/- 12% for both assays. The HPLC technique, however, has a greater linear response range of 10-600 mU CAT than the radioisotope method, which has a range of 10-400 mU CAT. The HPLC assay also requires a shorter assay time. As a result of this work we believe that HPLC is a viable alternative to the radioisotope-based assay described.

Cells, Cultured↗

PubMed2002

Radioisotope carrying polyethylene oxide-polycaprolactone copolymer micelles for targetable bone imaging.

The aim of this research is to develop polymeric micelle system as a targetable bone imaging carriers without nonspecific phagocytosis which is made of polyethylene oxide (PEO) and polycaprolactone (PCL). Diamino-PEO, which has two amino groups in its structure, was used to conjugate both PCL and ligand for specific radioisotope. PCL was conjugated to one amino group of diamino-PEO by using diaminohexyl cyclocarbodiimide (DCC), coupling agent. Hydroxyphenylpropionic acid (HPP), diethylenetriamine pentaacetic acid (DTPA) and mercaptoacetyl glycine glycidyl glycine (MAG3), as ligands for specific radioisotopes, were coupled to the rest of amino group of diamino-PEO by the same method as described. Formation of ligand-conjugated block copolymers, critical micelle concentration (CMC) of the copolymers, hydrodynamic radii, and morphology of the micelles were investigated. Besides, 125I-labelling efficiency and biodistribution of the micelles were examined. PEO-PCL block copolymer micelles demonstrated CMC of 25 mg/l and size of 60 nm, which may be adequate for blood vessel and bone imaging. 125I-labelling efficiency was above 90%, and was more stable at human serum for 24 h. 125I-labelled polymeric micelles showed higher blood maintenance and bone uptake when compared to stannous colloid, used as a control. A noticeable decrease in liver or spleen uptake could be achieved by the micelles. Therefore, radioisotope carrying PEO-PCL micelle system was suggested as a useful tool for effective diagnostic bone targeting and imaging.

Animals↗

PubMed2000

Using a non-radioisotopic, quantitative TRAP-based method detecting telomerase activities in human hepatoma cells.

A non-radioisotopic, quantitative TRAP-based telomerase activity assay was established mainly by using SYBR Green-I staining instead of radioisotope. Comparing with conventional radioisotope based method, it was better in reproducibility and accuracy. Using this method, we found telomerase activities were absent in normal human liver cells, while detected in all of four human hepatoma cell lines (BEL-7404, SMMC-7721, QGY-7903 and HCCM) without significant differences.

Animals↗

PubMed2001

Radioisotopic control for baclofen pump catheter failure.

STUDY DESIGN: Case report of Baclofen pump catheter failure investigated by radioisotope injection. OBJECTIVES: To report a safe and reliable method for evaluating catheter dysfunction. SETTING: France. METHODS: Single case report of failure of Baclofen pump investigated by radioisotope injection. RESULTS: The injection demonstrated the block in the catheter. The catheter failure was not visualised by plain X-ray nor by filling the pump with radio-opaque solution. CONCLUSION: Catheter failure is a common cause of intrathecal drug delivery problems and may be difficult to diagnose. When catheter disconnection, kink, or dislodgement is not visible on X-ray, radioisotopic control is a safe and reliable method for assessment.

Adult↗

PubMed2004

A low-dose radioisotope procedure for assessment of subcutaneous drug delivery systems used for slow intrathecal infusion of antispasmodic agents.

STUDY DESIGN: Retrospective single centre study. OBJECTIVES: To evaluate a low-dose radioisotope imaging procedure for assessment of implanted intrathecal drug delivery and to compare the radiation dose and diagnostic value of these studies with other reported studies using higher administered radiation dose. SETTING: National Spinal Injuries Centre, Stoke Mandeville Hospital, UK. METHOD: A total of 11 spinally injured patients with subcutaneous drug delivery systems and uncontrolled spasm were investigated for catheter failure using a low-dose radioisotope procedure with an administered dose of radioactivity of 40 MBq Technetium-99m. RESULTS: Loss of catheter patency was demonstrated in six patients, enabling identification of the site of blockage. Catheter patency and subsequent perfusion of CSF (ie normal result) was demonstrated in five patients. Radiation effective dose was estimated at 1.3 mSv per patient study, with a low associated risk of deleterious effect of one in 13,000. CONCLUSION: Radioisotope investigation using a reduced administered dose of 40 MBq Technetium-99m DTPA, formulated according to a strict radiopharmaceutical protocol, provides a safe test for assessment of intrathecal drug delivery systems.

Drug Delivery Systems↗

PubMed1994

Comparison of stable isotopes and radioisotopes in the measurement of iron absorption in healthy women.

1. Stable isotope methods are being used to investigate the absorption of dietary iron. In order to be certain that this new methodology is accurate, we have compared results obtained using stable isotopes and inductively coupled plasma mass spectrometry with those determined using a radioisotope and whole body counting. 2. The stable isotope 54Fe (2.8 mg) was given to 10 healthy non-pregnant women. Six women received the isotope in aqueous form, and four took it with a meat meal. The 54Fe served as a carrier for 10 ng of the radioisotope 59Fe. An ampoule (200 micrograms) of the isotope 57Fe or 58Fe was then given intravenously, and in serum samples taken over the next 10 h the ratios of the stable iron isotopes were measured by inductively coupled plasma mass spectrometry and the oral iron absorption was calculated. This was then compared with the results obtained by using a whole body counter to measure (on day 0 and day 14) the gamma-activity emitted by the radioisotope. 3. The mean iron absorption measured by both methods ranged from 8% to 45%. Measurement of the post-absorptive serum enrichment of the stable isotopes provided estimates of absorption from both aqueous and food iron which were similar to that yielded by whole body counting, the mean difference being -1.5% (95% confidence interval -5.2 to 2.1%). Absorption estimated by stable isotopes exhibited the same inverse relationship with the serum ferritin level (body iron stores) to that known to exist with whole body counting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1978

Artifactual radioassay results due to serum contamination by intravenous radioisotope administration. Falsely low serum vitamin B12 and folic acid results.

Radioisotopic contamination by recent radioisotope administration (either 99mtechnetium or 67gallium) to the patient for scanning purposes was found in 28 sera submitted for vitamin B12 or folic acid assay, or both, during the year prior to this study. In half the cases serum radioactivity was so great as to be readily identifiable during the assay. In the rest, however, the radioactivity would not have been detected had serum supernatant blanks not been routinely incorporated in the assay procedure. Many radioassay kits make no provision for such supernatant control blanks. Were it not for these blanks, five patients would have been falsely identified as vitamin B12-deficient and three others as possible deficient in the present series. Two of the five radioactive sera assayed for folate would also have given misleading results in the borderline-low range. The clinician should avoid ordering tests requiring radioassay when the patient has been given radioisotopes, and those performing radioassays must institute appropriate maneuvers to detect any such contamination.

False Positive Reactions↗

PubMed2004

Liquid chromatography-accurate radioisotope counting and microplate scintillation counter technologies in drug metabolism studies.

The present study involves an analysis of the performance of liquid chromatography (LC)-accurate radioisotope counting (ARC) and microplate scintillation counter (TopCount) technologies in drug metabolism studies. For the purpose of evaluating these systems, biological samples resulting from the metabolism of a radiolabeled [14C] compound, known as compound B, are analyzed using LC-ARC and TopCount under similar high-performance LC conditions. Counting efficiency is 83% for LC-ARC, 77% for TopCount, and linearity is R2 of 0.9998 versus 0.9984, respectively. The limit of detection for LC-ARC is 12 disintegrations per minute (dpm) with 1-min/fraction counting, yet for TopCount it is 8.7 dpm with 5-min/fraction counting. Under optimal conditions for each, the total run time of LC-ARC is approximately half that of TopCount. These results indicate that there is no significant difference between these two systems in terms of efficiency, linearity, and limit of detection. However, the LC-ARC system does not involve any manual operations, yet TopCount requires manual sample transfer and data import. This study shows that impressive progress has been made in the technology of radioisotope counting in drug metabolism using LC-ARC. This system enhances the resolution of radiochromatograms and is able to measure volatile metabolites that TopCount cannot detect at all. The ability to acquire mass spectra online is also a major advancement. The overall results suggest that the combination of LC-ARC with radioactivity detection and mass spectrometry has great potential as a powerful tool for radioisotope measurement in metabolite identification studies during drug discovery and development.

Chromatography, Liquid↗