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PubMed2003

Revealing smuggled nuclear material covered by a legitimate radioisotope shipment using CdTe-based gamma-ray spectrometry.

Illicit trade of nuclear materials (NM) represents a serious challenge to radiation monitoring upon scenarios, when legitimate radioisotope shipments are used to obscure the weak radiation of NM. Planar and hemispherical Cd(Zn)Te detectors with a portable mini-multichannel analyzer were proven to be suitable, in measuring times of 10min order, for revealing the presence of low-enriched or natural U-bearing reactor fuel pellets in amounts of kg order, placed beside transport containers of lead or depleted uranium, which contain high activity 60Co (10GBq range) or 192Ir (TBq range) radioisotope sources. Such a hand-held or portable device may help authorities combating illicit trafficking of nuclear materials.

Equipment Design↗

PubMedDate not supplied

Endovascular beta irradiation for prevention of restenosis using solution radioisotopes: pharmacologic and dosimetric properties of rhenium-188 compounds.

PURPOSE: Irradiation of the arterial wall with beta particles has been shown to be effective in inhibiting neointimal hyperplasia following percutaneous transluminal coronary angioplasty (PTCA). In this study, we describe the use of 188W/188Re generators to obtain 188Re (half-life 16.9 h, maximal beta energy of 2.12 MeV) as a new candidate radioisotope for endovascular irradiation. We have evaluated two [188Re]-compounds as candidates for use as solution-based radiation sources that would allow conventional liquid-filled balloon inflation for delivery of radiation to the vessel wall. While balloon rupture at nominal inflation pressures is a very rare event, (<1 per 10,000 at high pressure), radioisotope release could potentially result in significant dose to radiation-sensitive organs. We have thus evaluated the biodistribution, dosimetry, and kinetics of excretion in rats of two 188Re-labeled compounds that are proposed for intravascular therapy. MATERIALS AND METHODS: Rhenium-188 was obtained as [188Re]-sodium perrhenate by saline elution of an alumina-based 188W/188Re generator system (>500 mCi). High specific volume solutions of the [188Re]-sodium perrhenate (>50 mCi/ml) were obtained by post-elution concentration of the generator bolus by passage through a tandem silver cation/anion column system. Rhenium-188-labeled benzoylthioacetyltriglycine (MAG3) was prepared by stannous ion reduction of [188Re]-perrhenate in the presence of the benzyl-MAG3 substrate, and was characterized as a single radioactive component. Rhenium-188-perrhenate and [188Re]-MAG3 were administered to separate groups of Fischer rats, which were sacrificed at various times and the tissue distribution of 88Re determined in the major organs. Excretory products were also collected daily from separate groups of rats for each agent over 7 days. The effects of perchlorate and iodide preblocking and postdisplacement of thyroid uptake of [188Re]-perrhenate were also evaluated. RESULTS: Organ uptake values were modest for both agents [<0.25 % injected dose(ID)/gram of tissue at 6 h] for all organs evaluated except for the thyroid, with the intestines and intestinal contents showing the highest uptake values (0.72-1.97 %ID/gram). Whereas thyroid uptake of 188Re after injection of [188Re]-MAG3 was low (0.16 %ID/gram), uptake after injection of [188Re]-perrhenate was higher and could be blocked by pretreatment with perchlorate (intravenous [IV]) or displaced by perchlorate posttreatment. Also, oral or IV iodide pre- or postadministration could also significantly block or displace thyroid uptake of [188Re]-perrhenate. Both [188Re] agents were excreted primarily via the urinary bladder. The excretion half-life of [188Re]-perrhenate was about 7 h; in contrast, the [188Re]-MAG3 complex showed 50% excretion in less than 2 h. The large intestines received the most significant adsorbed dose, with values of 2.0 cGy/ mCi for [188Re]-perrhenate and 4.6 x 10(-3) cGy/mCi for [188Re]-MAG3. CONCLUSIONS: Rhenium-188-MAG3 shows more rapid urinary bladder excretion in rats than perrhenate and both agents show low organ uptake. Thyroid uptake of free [188Re]-perrhenate can be blocked or displaced with oral perchlorate administration. For the projected use of [188Re]-MAG3 for balloon inflation required for irradiation of the arterial wall, calculated organ dose values are within acceptable limits in the unlikely event of low pressure balloon rupture. Rhenium-188-MAG3 in solution is thus a new candidate for balloon dilation providing uniform endovascular irradiation following PTCA for restenosis therapy.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

Conditionally cleavable radioimmunoconjugates: a novel approach for the release of radioisotopes from radioimmunoconjugates.

One of the limitations of therapy with radiolabeled monoclonal antibodies (mAbs) is that significant toxicities can arise from circulating non-tumor-bound radiolabeled conjugate. Here, we describe a new method to reduce systemic radiation exposure from radiolabeled mAbs involving the attachment of the radioisotope through a linker that can be cleaved by an administered enzyme. To demonstrate the feasibility of this approach, we prepared a conditionally cleavable radioimmunoconjugate (RIC) composed of (131)I-labeled cephalosporin conjugated to Tositumomab, a mAb against the CD20 antigen. The cleavable RIC bound antigen identically to directly iodinated antibody, and in the presence of beta-lactamase, about 80-85% of the radioisotope was released. In vivo studies in mice revealed that the cleavable RIC and the directly iodinated anti-CD20 antibody had similar biodistribution patterns. Systemically administered beta-lactamase induced a 2-3-fold decrease in the percent injected dose (ID) of the cleavable RIC/g of blood, marrow, spleen, lung, and liver 1 h after enzyme treatment, and a 4-6-fold decrease 20 h after enzyme treatment. This was accompanied by a 20-fold increase in % ID/g in urine 1 h after enzyme treatment, indicating that the released radiolabel was rapidly excreted through the kidneys. In mice with human tumor xenografts, there was no decrease in the %ID/g in tumor 1 h after enzyme treatment, but by 4 h after enzyme injection, decreases in tumor radioactive content began to diminish the targeting advantage. These studies demonstrate that the cleavable RIC substrate is able to bind to tumor antigens and localize within human tumor xenografts and that accelerated systemic clearance can be induced with beta-lactamase.

Animals↗

PubMedDate not supplied

Radioisotope CSF flow studies in leptomeningeal metastases.

BACKGROUND: Leptomeningeal metastases is a frequent neuro-oncologic complication in patients with cancer. OBJECTIVE: Radionuclide CSF flow studies provide a unique method of evaluating CSF compartments in patients with leptomeningeal metastases. METHODS: Radionuclide CSF flow studies are performed by injecting (111)Indium-DTPA into either the ventricular or lumbar CSF compartment. (111)Indium-DTPA is entrained by CSF and flows through CSF compartments based on normal CSF physiology. RESULTS: Normal times to appearance of (111)Indium-DTPA following intraventricular injection in either adults or children are as follows: ventricles (median 1 minute); cisterna magna/basal cisterns (5); cervical (15); thoracic (20); and lumbar (30) spinal subarachnoid spaces; and sylvian cisterns (50). Normal times to appearance of (111)Indium-DTPA following intralumbar injection are as follows: lumbar (1); thoracic (22.5); cervical (32.5) spinal subarachnoid spaces; cisterna magna/basal cisterns (37.5); sylvian cisterns (65); ventricles (1,440); and cerebral convexities (1,440). In 30 consecutive patients, 47% of patients had documented compartmentalization of CSF by (111)Indium-DTPA CSF flow studies. 13% had base of brain obstruction of whom 50% responded with re-establishment of normal CSF flow and 33% had spinal subarachnoid space block of whom 40% following therapy had re-establishment of normal CSF flow. In 61 consecutive patients, 33% of patients had abnormal spinal CSF flow studies which better demonstrated interruption of CSF flow when compared to CT myelography and spine MR. In 40 patients, all with CSF block, 20 of whom responded to therapy with re-establishment of normal CSF flow as compared to 20 with refractory CSF block, significant differences were seen in median survival and cause of death favoring patients with normal or restored CSF flow. CONCLUSIONS: Radioisotope CSF flow studies in patients with leptomeningeal metastasis appear to have two practical uses. First, radioisotope CSF flow studies by documenting normal CSF flow predict for homogeneous distribution of intra-CSF chemotherapy. Secondly, in patients with CSF flow obstruction refractory to site of obstruction therapy, limited survival, rapid leptomeningeal disease progression and death due to progressive CNS disease is predicted.

Adult↗

PubMed2002

Research and development of a radioisotope dose calibrator with background alarm used in nuclear medical laboratories.

In this study, research and development of a prototype background alarm levelled radioisotope dose calibrator for nuclear medical laboratories was emphasized. The aim was to develop a standard performance, economical dose calibrator (self-made) from the ion-chamber to the microcomputer. Dose calibrators are used in nuclear medical laboratories for treatment and diagnosis purposes. The device is developed using an ion chamber filled with 2 atm pressure argon gas, 3N201 dual gate mosfet for the extremely high impedance preamplifier, an Intel 8052AH microcontroller for the microcomputer, ADC0804 for the A/D conversion, a Phillips 2 x 16 character display, and other components. Correction factors are used for each radioisotope after the activity measurements, that can be updated and kept in the Ni-Cd rechargeable battery-powered RAM memory. To provide safety in nuclear medical laboratories, background activity values are measured.

Calibration↗

PubMed2003

The rat sodium iodide symporter gene permits more effective radioisotope concentration than the human sodium iodide symporter gene in human and rodent cancer cells.

Expression of the sodium iodide symporter (NIS) gene in tumor cells may provide a novel mechanism for treating cancer. The NIS mediates the normal physiological transport of iodide across the thyroid cell membrane. This mechanism of iodide uptake has been used to both diagnose and treat thyroid cancer. Tissue expression of the NIS is largely limited to the thyroid; therefore, expression of the NIS gene in cancer cells would allow for specific iodine uptake, radioisotope accumulation, and treatment. In this study, we directly compared the human and rat NIS (rNIS) for their ability to concentrate radioisotope into human and rodent cancer cells. Perchlorate-sensitive (125)I uptake in multiple cell lines was demonstrated following transduction with retroviral vectors expressing either the human or rNIS gene. Surprisingly, iodine uptake was consistently higher with the rNIS gene, up to 5-fold greater, when compared to the human gene, even within a variety of human tumor cell lines. This iodine uptake allowed for cell killing following (131)I treatment in NIS-transduced cells when assayed by in vitro clonogenic assays. These results demonstrate that the rNIS gene provides superior iodine uptake ability, and may be preferable for use in designing anticancer gene therapy approaches.

Animals↗

PubMed1968

The estimation of galactose, mannose and fucose in glycoproteins by radioisotope dilution.

1. The principle of radioisotope dilution, as used previously for the estimation of mannose in egg albumin, was applied on a semi-micro scale to the estimation of fucose, mannose and galactose in some glycoproteins. The sugars were separated by partition chromatography on columns of Celite 545. 2. The release of mannose from egg albumin in 2n-hydrochloric acid at 100 degrees after various times was determined by the radioisotope-dilution method and found to have a half-time of 7min. 3. The destruction of mannose in 2n-hydrochloric acid after 3hr. at 100 degrees was found to be small if air was excluded. The destruction was slightly increased by the presence of lysozyme containing tryptophan in an amount equimolar with the mannose. The same amount of free tryptophan caused considerable loss of mannose. 4. Analytical values are reported for the non-amino sugar contents of egg albumin, rabbit gamma-globulin and some samples of blood-group-specific substances. The values found were similar to the most reliable estimates published previously.

Animals↗

PubMed1989

A unified design algorithm of two-dimensional digital filters for radioisotope image processing.

A unified design algorithm of two-dimensional digital filters for radioisotope image processing based on the Fourier-Bessel transform and the weighted least-squares method is described. The algorithm presented here can treat the various kinds of two-dimensional digital filters in a unified approach. Design examples are presented and several graphs are included to show the relationships between the design parameters as an aid in practical applications. The application of the method in radioisotope image processing is also presented. Several low-pass, Wiener and band-pass filters were designed using the method and applied to some clinical data in nuclear medicine including SPECT images. The digital filter design technique proposed here is considered to provide a powerful tool for extraction of additional qualitative information and improvement of the quality of nuclear medicine images both in research and in routine clinical work.

Algorithms↗

PubMed1976

Radioisotopic assay of vitamin B12 in tissues.

The present study delineates the application of the radioisotopic competitive-inhibition assay for the measurement of vitamin B12 in tissues. The extraction of endogenous B12 from tissues was shown to be simple and complete. Proportional dilution studies suggest that tissue factors do not interfere with the assay. Although some variability exists when multiple areas of an organ are sampled, the differences between B12 levels in tissues obtained from normal individuals and B12-deprived individuals are so wide that individual intra-organ variability is trivial, As this tissue B12 assay is similar to the widely utilized radioisotopic assays for serum B12, it is applicable for routine use.

Animals↗

PubMed1983

Biological elimination rates of radioisotopes by mallards contaminated at a liquid radioactive waste disposal area.

The biological elimination of nine gamma-emitting radioisotopes was studied in mallards (Anas platyrhynchos) which were released onto liquid radioactive waste pounds in southeastern Idaho. After 68, 75 or 145 days, the ducks were removed from the contaminated environment and placed in metabolic cages. Whole-body and feces-urine counts were made for 51 days and then the ducks were sacrificed and dissected for tissue analyses. The biological elimination of radioisotopes were fit to two compartment models using non-linear least squares estimation. Fecal-urine data substantiated two-compartment elimination of all radionuclides. Biological half-lives in mallards were 10 days (131I), 22 days (140Ba), 86 days (51Cr), 32 days (58Co), 26 days (75Se), 67 days (65Zn), 10 days (134Cs), 67 days (60Co) and 11 days (137Cs). Body burdens in ducks were at 90% of equilibrium with the radioactive waste pond water at the time of removal from the waste ponds. Tissue distribution of radionuclides on the day of removal from the ponds showed gut to have the highest concentrations followed by feather, liver and muscle. After 51 days in metabolic cages, feather had the greatest radionuclide concentrations followed by liver, muscle and gut. Liver contained the greatest variety of radionuclides and muscle the smallest. Biological elimination rates for the major dose-contributing nuclides (134Cs and 137Cs) to humans consuming contaminated waterfowl tissue indicate that the dose to man could be reduced substantially due to the rapid elimination of these radionuclides by mallards. Contaminated waterfowl would receive most of the internal dose in the first month after leaving the contaminated environment indicating that long-term doses would be inconsequential.

Animals↗

PubMed1996

Radiosensitization with low-dose carboplatin enhances pain palliation in radioisotope therapy with strontium-89.

Strontium-89 (89Sr) is currently used for the treatment of painful bone metastases. This study reports the use of low-dose carboplatin as a radiosensitizer in 89Sr radioisotope therapy. The study design comprised two groups: 15 patients treated with 89Sr (148 MBq) followed by carboplatin (100 mg m-2 at 7 and 21 days) and 15 patients treated with 89Sr alone. Their pain response was assessed 8 weeks post-injection. Follow-up was continued for up to 1 year in the survivors. Twenty-seven patients were evaluable. A pain response was observed in 20 of 27 (74%) patients. The pain response in the patients treated with 89Sr and carboplatin was clearly superior to that seen in the patients treated with 89Sr alone (P = 0.025), whereas survival was only marginally better in the combined treatment group (8.1 vs 5.7 months, P = 0.19). No clinically significant adverse effects or myelosuppression by carboplatin were observed. Low-dose carboplatin enhances the effects of 89Sr radioisotope therapy on pain from bone metastases.

Adult↗

PubMed1989

Radioisotope studies in monitoring of Gaucher's disease and its treatment.

Radioisotope studies (blood volume, spleen function, and ferrokinetics) were performed in seven patients with chronic (type 1) Gaucher's disease. Interestingly, the 52Fe scans and spleen histology demonstrated extramedullary haemopoiesis in the liver and spleen. Radioisotope measurements (red cell volume, plasma volume, red cell pool, damaged cell clearance, spleen blood flow, 59Fe clearance, red cell utilization and 52Fe scans) provide methods for accurate measurement of the bone marrow and spleen function, thereby enabling prediction of the most suitable time for splenectomy, in the treatment of patients with Gaucher's disease.

Gaucher Disease↗

PubMed2006

Long-term evaluation of radioisotope synovectomy with Yttrium 90 for chronic synovitis in Turkish haemophiliacs: Izmir experience.

Since 2001 we have performed 105 radioisotope synovectomy (RS) in 65 children and young adults, age ranging from 3 to 25 years with a average of 15 years in Ege University Hospital, Izmir, Turkey. One fourth of cases were below 10 years of age. All patients had severe haemophilia A and B. Ten patients (17 joints) had high responder inhibitor. We prefer to use Yttrium 90 for all joints (5 mCi for knees; 2 mCi for others). The knees were injected in 56 cases, elbows in 24 cases, ankles in 23 cases and shoulders in two cases. Steroid injections were not preferred as the principle drug of choice. Mean follow-up period after procedure was 2 years (range: 6 months to 3.5 years). All inhibitor patients had satisfactory results. The best results were obtained in elbows than knees and ankles. Excellent rates (no bleeding) were observed in grade-II synovitis 84% for knees, 93% for elbows and 50% for ankles. Because of the excellent and good response (bleeding reduction to 75%), rates were 100% for knees and elbows and 92% for ankles. In six cases, repeated injections were given at 6-month interval and all of them had good results. The grading of synovitis seems to be an important parameter than the age of the patient. Even in patients below 10 years of age, outcomes are not satisfactory in all joints with grade-III vs. grade-II synovitis (12% vs. 73%). No serious complications were observed during and after procedure except two cases. A mild and transient inflammatory reaction was observed in the ankle. There was a minimal radioisotope leakage to superficial skin in the elbow. RS seems to be a safe and effective treatment for chronic synovitis causing recurrent joint bleedings.

Adolescent↗

PubMed1983

Prospects for using implanted systems of assisted circulation and artificial heart with a radioisotope power source (biomedical, thermal, and radiation aspects).

The capacity of dogs to diffuse heat (up to 50 W) from an artificial heart and to tolerate prolonged intracorporeal ionizing radiation from a radioisotope power source (238Pu) was investigated, using electrical models of vascular blood heat exchangers that permit reproduction of elimination and heat transmission in autonomous systems. It was shown that up to 50 W can be discharged at temperatures of the wall-blood interface that do not exceed 43 degrees C. Clotting indexes, concentration of total protein, hemolysis, and serum enzyme activity during 1-1.5 months of heating remained within physiologically normal limits. A specific power load of up to 1.5 W/kg at ambient temperatures of 18-20 degrees C revealed no evidence of changes in heat production. By measuring the distribution of power of the dose absorbed around a 45-W plutonium source it was possible to estimate dose loads on critical organs and to assess overall risk of death from malignant tumors induced by radiation over a 10-year period: 6-12% for males and 8-14% for females. It is not very probable that use of the artificial heart with a radioisotope power source will be limited by thermal and radiational effects.

Animals↗

PubMedDate not supplied

A first estimate of ground water ages for the deep aquifer of the Kathmandu Basin, Nepal, using the radioisotope chlorine-36.

The Kathmandu Basin in Nepal contains up to 550 m of Pliocene-Quaternary fluvio-lacustrine sediments which have formed a dual aquifer system. The unconfined sand and gravel aquifer is separated by a clay aquitard, up to 200 m thick, from the deeper, confined aquifer, comprised of Pliocene sand and gravel beds, intercalated with clay, peat, and lignite. The confined aquifer currently provides an important water supply to the central urban area but there are increasing concerns about its sustainability due to overexploitation. A limited number of determinations of the radioisotope 36Cl have been made on bore waters in the basin, allowing us to postulate on the age of ground water in the deeper, confined aquifer. Ground water evolution scenarios based on radioisotope decay, gradual dissolution of formational salts as the ground waters move downgradient, and flow velocity estimations produce comparable ground water ages for the deep waters, ranging from 200,000 to 400,000 years. From these ages, we deduce a mean ground water flow velocity of only 45 mm/year from recharge in the northeast to the main extraction region 15 km to the southwest. We thus estimate current recharge at about 5 to 15 mm/year, contributing 40,000 to 1.2 million m3/year to the ground water system. Current ground water extraction is estimated to be 20 times this amount. The low specific discharge confirms that the resource is being mined, and, based on current projections, reserves will be used up within 100 years.

Chlorine↗

PubMed1966

Comparison of the radioisotope dilution-coated charcoal method and a microbiological method (L. leichmannii) for measuring vitamin B12 in serum.

A comparison has been made of the radioisotope dilution-coated charcoal method and a microbiological assay (with L. leichmannii as test organism) for determining the concentration of vitamin B(12) in serum. A satisfactory correlation was found between the results of the two methods. Under appropriate conditions the reproducibility of the radioisotope method compared favourably with that of the microbiological method.

Biological Assay↗

PubMed1992

Model equations for condensation biosynthesis using stable isotopes and radioisotopes.

Important syntheses in living systems occur by condensation reactions of the type nA----1B (where n is the number of A molecules needed to synthesize 1 molecule of B). Quantitative relationships for estimating the rate of synthesis of B from radioactive and stable isotope tracers are compared. With radioisotope tracers, only a single quantity is detected, the amount of radioactivity in B. In contrast, isotopes of varying mass produce multiple mass isotopomers B that are detected using mass spectrometry. The analysis demonstrates that the rate of synthesis of B is identifiable from stable isotope data but not from radioisotope data. This results because the isotopomer distribution of B at any time after tracer addition is a function of only the multinomial distribution representing the synthesis of B from n molecules of A and two parameters representing the fractional fluxes of isotopically enriched molecules to the sampled compartment of B. The model considers the possibility that the sampled compartment of B may not reach isotopic steady state during the experiment. A graphical method for obtaining initial estimates of the two parameters is presented.

Acetates↗

PubMed1995

H2O2 determination in rat lens: chemiluminescent versus radioisotopic methods.

Hydrogen peroxide levels have been determined in rat lenses by using two methods, a chemiluminescent and a radioisotopic method. The average content was found to be 155 +/- 20 and 127 +/- 18 nmol/g wet weight of the tissue, respectively, by the two methods. The reaction of H2O2 with dichlorophenol-indophenol in the presence of peroxidase was also studied. However, this was found to be less suitable. The results of the chemiluminescent determinations are similar to the results with the radioisotopic methods demonstrating the feasibility of determining H2O2 by chemiluminescence measurement as well.

2,6-Dichloroindophenol↗