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Deposition of (90)YPO(4) and (144)CePO(4) radioisotopes on polymer surfaces for radiation delivery devices.

Intravascular irradiation with beta emitters inhibits restenosis in arteries after balloon angioplasty or stent implantation. Yttrium-90 ((90)Y, T(1/2)=64 h) and cerium-144 ((144)Ce, T(1/2)=286 d) emit beta particles (E(max)=2.28--3.50 MeV) having an ideal energy range for brachytherapy delivery system. In this article, a previously reported method for depositing (32)P on poly(ethylene terephtalate) (PET) surfaces is generalized and modifications that allow deposition of other beta-emitting radioisotopes, such as (90)Y and (144)Ce, are demonstrated. PET films were first coated with chitosan hydrogel and then adsorbed different amounts of phosphoric acid (PA) in aqueous solutions. Yttrium was deposited onto the surface as YPO(4) after the films were immersed in YCl(3) solutions. 1 muCi (90)YCl(3) (2 x 10(-9) g) was used in each sample as a tracer for measuring the deposition efficiency, which is defined as the percentage of YCl(3) deposited on the surface compared to the amount of YCl(3) in solutions before the deposition. In order to improve the safety of brachytherapy treatments, polyurethanes were used to seal the deposited radioisotopes on the surface to minimize the leakage of the isotopes into the patients. The generality of this method presented here for a wide variety of particular radioisotopic components allows design of a broad range of versatile radioisotope sources.

Brachytherapy↗

Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study.

Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.

Creatinine↗

A novel dual radio- and stable-isotope method for measuring calcium absorption in humans: comparison with the whole-body radioisotope retention method.

BACKGROUND: Dietary calcium absorption can be determined only with the use of isotope techniques. Currently used isotope techniques require exclusive equipment or are not true tracer approaches. OBJECTIVE: The objective was to compare a dual-isotope method combining radioisotopes and stable isotopes with a whole-body radioisotope retention method for measuring calcium absorption. DESIGN: Seven healthy adults aged 21-27 y consumed a test meal containing 63 +/- 14 (macro x +/- SD) mg Ca together with a water solution of (47)Ca (0.11 MBq). One hour after ingestion, 18 mg (44)Ca was administered intravenously. All feces and urine were collected for 5 and 6 d, respectively. Calcium absorption was estimated from whole-body retention of the radioisotope 12 times over 3 wk after ingestion and from the excretion of (47)Ca and (44)Ca in a 24-h urine sample collected on day 2. (44)Ca in urine was determined by inductively coupled plasma mass spectrometry. RESULTS: Mean (+/- SD) calcium absorption was 75 +/- 9% with the dual-isotope method and was 74 +/- 8% with the whole-body radioisotope retention method. There was a high degree of agreement between the methods. CONCLUSION: The dual-isotope method is a valid approach for measuring calcium absorption from a single meal.

Administration, Oral↗

[Radioisotope methods and technics in obstetrical and gynecological diagnosis].

Certain applications of radioisotopes to obstetric and gynaecological diagnosis are illustrated. Radioisotopes have been widely employed since the improvement in instrumental methods and the availability of short-life radioisotopes has removed the basic limitation which once prevented their use during the entire fecund period of the woman owing to the risk of radiation damage to the reproductive system. Particular attention is paid to the advances made in placental localization, in the study of thyroid and renal function in pregnancy, in the study of the diffusion of female genital tumours and relapses, and in early diagnosis of tumours of the uterus and ovaries. Dosimetric problems arising when using diagnostic techniques with radioisotopes in obstetrics and gynaecology are analysed.

Adult↗

A new constant infusion radioisotopic technique for the noninvasive determination of cardiac output.

A constant infusion radioisotopic method for the noninvasive determination of cardiac output is introduced and validated in a series of 22 patients by comparison with simultaneous dye dilution or Fick measurements. The new bedside radioisotopic technique utilizes peripheral venous infusion of indium-113m, detection by a single external probe, and analysis of the time-concentration curve by a specially designed, multivariate computer model. The technique is entirely atraumatic, requiring neither injection into the central circulation nor intra-arterial cannulation. The correlation coefficient was 0.72 (p less than 0.001) between the radioisotopic and standard methods for cardiac output determinations. In addition, results in five patients with valvular regurgitation or intracardiac shunts support the validity of the constant infusion radioisotopic technique in these clinical settings in which the standard dye dilution methods for determining cardiac output are invalid. The techniques is applicable in a variety of clinical conditions in which the invasive techniques for cardiac output measurement are either impractical or not available.

Adult↗

In vivo quantitation of intratumoral radioisotope uptake using micro-single photon emission computed tomography/computed tomography.

PURPOSE: This study was undertaken to determine the ability of micro-single photon emission computed tomography (micro-SPECT)/computed tomography (CT) to accurately quantitate intratumoral radioisotope uptake in vivo and to compare these measurements with planar imaging and micro-SPECT imaging alone. PROCEDURES: Human pancreatic cancer xenografts were established in 10 mice. Intratumoral radioisotope uptake was achieved via intratumoral injection of an attenuated measles virus vector expressing the NIS gene (MV-NIS). On various days after MV-NIS injection, (123)I planar and micro-SPECT/CT imaging was performed. Tumor activity was determined by dose calibrator measurements and region-of-interest (ROI) image analysis. Agreement and reproducibility of tumor activity measurements were assessed by Bland-Altman plots and Lin's concordance correlation coefficient (CCC). RESULTS: Intratumoral radioisotope uptake was detected in all mice. Scatterplots demonstrate strong agreement (CCC = 0.93) between micro-SPECT/CT ROI image analysis and dose calibrator tumor activity measurements. The differences between dose calibrator activity measurements and those obtained with ROI image analysis of micro-SPECT alone and planar imaging are less accurate and more variable (CCC = 0.84 and 0.78, respectively). CONCLUSIONS: Micro-SPECT/CT can be used to accurately quantify intratumoral radioisotope uptake in vivo and is more reliable than planar or micro-SPECT imaging alone.

Animals↗

Analysis of metal radioisotope impurities generated in [(18)O]H(2)O during the cyclotron production of fluorine-18.

We show the separation of metal radioisotope impurities using capillary electrophoresis (CE). The methodology used is an improvement of existent protocols for separation of stable metal ions. Production of fluorine-18 using [(18)O]H(2)O-enriched water encased in a titanium target body results in the production of several metal radioisotope impurities. Optimisation of the conditions for CE separation of the metal radioisotope impurities incorporated the use of 6 mM 18-Crown-6 in combination with 12 mM glycolic acid as complexing agents within the running buffer (10 mM pyridine, pH 4.0). Using this optimised procedure, we were able to separate and detect a number of metal radioisotopes, including chromium, cobalt, manganese, vanadium and berillium, within the fM concentration range.

Cyclotrons↗

A simple and selective method for the separation of Cu radioisotopes from nickel.

Separation of copper radioisotopes from a nickel target is normally performed using solvent extraction or anion exchange rather than using cationic exchange. A commonly held opinion is that cationic exchangers have very similar thermodynamic complexation constants for metallic ions with identical charges, therefore making the separation very difficult or impossible. The results presented in this article indicate that the selectivity of Chelex-100 (a cationic ion exchanger) for Cu radioisotope and Ni ions not only depends on the thermodynamic complexation constant in the resin but also markedly varies with the concentration of mobile H+. In our developed method, separation of copper radioisotopes from a nickel target was fulfilled in a column filled with Chelex-100 via controlling the HNO3 concentration of the eluent, and the separation is much more effective, simple and economical in comparison with the common method of anion exchange. For an irradiated nickel target with 650 mg Ni, after separation, the loss of Cu radioisotopes in the nickel portion was reduced from 30% to 0.33% of the total initial radioactivity and the nickel mixed into the radioactive products was reduced from 9.5 to 0.5 mg. This significant improvement will make subsequent labeling much easier and reduce consumption of chelating agents and other chemicals during labeling. If the labeled agent is used in human medical applications, the developed method will significantly decrease the uptake of Ni and chelating agents by patients, therefore reducing both the stress on human body associated with clearing the chemicals from blood and tissue and the risk of various types of acute and chronic disorder due to exposure to Ni.

Chromatography, Ion Exchange↗

The beta-particle-emitting radioisotope stent (isostent): animal studies and planned clinical trials.

Radiation delivered by intravascular stent is an appealing approach to prevent neointimal hyperplasia, since it nonselectively kills dividing cells. In particular, beta-particle-emitting radioisotope stents may prove to be an ideal means of local irradiation in that 95% of the dose is delivered within 4 mm of the stent edge and the dose drops off rapidly to < 1/1,000 of the original dose at 5 months postimplantation. In the in vitro smooth muscle cell model, one can observe a zone of growth inhibition around radioactive stent wires that averages about 6 mm at very-low-activity levels (0.006 microCi/cm of wire). In vivo studies in animal models, including porcine iliac and coronary arteries and rabbit iliac arteries, have shown the effectiveness of radioisotope stents in inhibiting neointimal proliferation. Proliferating endothelial cells appear to be relatively radioresistant. A computer model was employed to look at the radiation dose delivered as a function of distance from the stent. With very-low-activity stents, presumably, DNA of the smooth muscle cells is damaged as they migrate through the "electron fence" on the way to the neolumen, diminishing the population of myofibroblasts and reducing hyperplasia. Catheter-based radiation therapies may disable these cells before they migrate, although such an approach may not inhibit early recoil or late contraction. Based on the characteristics of beta emissions (i.e., rapid drop-off, minimal leaching), radioisotope stents containing phosphorus-32 appear to be safe. A randomized triple-blind clinical trial is planned to assess restenosis at 6 months in native coronary arteries treated with radioisotope stents.

Animals↗

Relationship between the radioisotope test using 131I-labelled serum albumin and plethysmographic blood flow measurements in the study of the circulation in the foot.

A radioisotope test using 131I-labelled serum albumin and venous occlusion plethysmography were performed simultaneously on the feet of normal individuals and patients with peripheral arterial disease during a period of reactive hyperemia. The radioisotope test includes a circulation time and a build-up curve reflecting a local clearance process which is characterized by the parameter M/2 -- delay. Between the parameter M/2 -- delay of the radioisotope test and the blood flow measured by the plethysmograph, the power relationship was found to be: M/2 -- delay = 74.01 F-0.74 with r = 0.69. The experimental data show that the plethysmographic blood flow measurement is an accurate method for the assessment of the peripheral circulation in normal individuals but is less suitable in patients with peripheral arterial disease. The radioisotope test appears to be more valuable than the plethysmographic blood flow measurement for the differentiation of normal individuals from patients with peripheral arterial disease and for the evaluation of the grade of ischemia.

Adult↗

[Role of radioisotopic lymphoscintigraphy in postphlebitic syndrome of the legs].

Post-phlebitis syndrome of the lower limbs is a set of symptoms that follow a state of phlebostasis and phlebolymphostasis with consequent oedema and tissue distress. We submitted 36 patients with post-phlebitis syndrome of the lower limbs to radioisotopic lymphoscintigraphy for the purposes of evaluating the vicariant function of the lymphatic system and the possible role of the lymphatic system in the genesis of dermo-epidermal abnormalities. The average age of the patients was 53.2 years (range: 43-69 years; M:F ratio: 0.50). The control group consisted of 6 healthy subjects. The average duration of the post-phlebitis syndrome in the patients studied was 8.5 years. We excluded from the study patients in whom a central cause was identified as being responsible for the pathogenisis of the oedema of the lower limbs. In addition, patients with obliterant arteriopathy were also excluded. Venous pathology was evaluated first clinically and then investigated by continuous-wave Doppler. As a first step, venous pressure was measured by Doppler phlebomanometry in clino- and orthostatism. All patients underwent radioisotopic lymphoscintigraphy with microcolloids using the Rijke technique. Radioactivity was monitored by means of a computerized gamma-camera. We classified the pathological findings of radioisotopic lymphoscintigraphy as follows: 1) delayed transit; 2) obstacles; 3) star-shaped superficial collateral lymphatic circulations; 4) lymphocoele or cutaneous lakes. A significant difference was detected (p < 0.05) between the pressure values in the post- phlebitis lower limbs and the pressure values in normal subjects. Combining the results of our measurements we recorded delayed transit in 5 patients (69.5%). This latter group included the cases with the severest forms of post-phlebitis syndrome. Therefore, better knowledge of the pathophysiology of the lymphatic system would appear to be useful in order to understand the origin and evolution of oedema of the lower limbs of patients with post-phlebitis syndrome. To this end, radioisotopic lymphoscintigraphy may be useful as a first-level examination in order to evaluate the capacity and efficiency of the lymphatic system.

Adult↗

Application of radioisotope renography with technetium-99m mercaptoacetyltriglycine on patients with spinal cord injuries.

The effectiveness of radioisotope renography with Technetium-99m (Tc-99m) mercaptoacetyltriglycine (MAG3) to provide possible routine urological follow-up was evaluated for the spinal cord injury (SCI) population. Sixty-six SCI patients were examined with radioisotope renography and renal ultrasonography. Excretory urography was done on 46 patients and voiding cystourethrography was done on 46 patients and voiding cystourethrography was done on 59 patients. The time-activity curve patterns of renography were classified into six groups. Curves A were normal. Curves B and C showed various excretion delay but normal effective renal plasma flow (ERPF). Curves D, E, and F showed definite decreased ERPF and excretion delay of different severity. The respective incidence of upper urinary tract complications were 12.0% (10/83) for A, 68.2% (15/22) for B, 100% (4/4) for C, 100% (8/8) for D, 100% (11/11) for E, and 100% (4/4) for F curves. The sensitivity of radioisotope renography was 83.9%, and the specificity was 92.0% in detecting the upper urinary tract complications. There was no adverse effect after 80 renography examinations on 66 SCI patients. As excretion delay occurred in the earlier stage of renal dysfunction, followed by decrease of ERPF, the abnormal time-activity curves can be sensitive indicators to subject SCI patients with early renal deterioration for further urodynamic and morphological studies. For patients with normal renograms, conventional uroradiological studies are not recommended because they are more invasive, cumbersome, and have more side effects as well as higher radiation exposure. We found that radioisotope renography with Tc-99m MAG3 is a safe, noninvasive, sensitive, and valuable urological screening test for SCI patients.

Adolescent↗

[Correlation between gastrointestinal absorption and uptake of radioisotopes by the critical organs].

This study was undertaken to investigate the correlation between gastrointestinal absorption of radioisotopes and uptake by the critical organ during the same period using 85Sr, 109Cd, 131I and 203Hg as radioisotopes. When the distribution of 85Sr, 109Cd, 131I and 203Hg in mice were investigated by means of the whole body autoradiography, these critical organs were determined as follows; 85Sr: bone, 109Cd: liver, 131I: thyroid gland and 230Hg: kidney. When the correlation between the injected dose and the uptake dose by the critical organ of 85Sr, 109Cd, 131I and 203Hg were investigated, uptake dose the critical organ expressed as cpm per gram of organ was in direct proportion to the injected dose and that expressed as % of the injected dose per gram of organ was held constand in either case. When the coefficient of correlation between gastrointestinal absorption and uptake by the critical organ of 85Sr, 109Cd, 131I and 203Hg were calculated, a positive correlation was revealed in either case. It is concluded from the results obtained that in vivo or in situ method, gastrointestinal absorption of radioisotopes received a support from uptake by the critical organ during the same period.

Animals↗

[Decontamination effectiveness of Ca-, Zn- and MnDTPA chelates in internal contamination with Cs-137, Ce-144, J-131, Sr-90 radioisotopes].

The studies were carried out on 240 rabbits divided into 4 groups, in which, after contamination with i.v. radioisotopes 137Cs (A), 144Ce (B), 131J (C), 90Sr (D), Ca-, Zn-, MnDTPA chelates were used in 12.5% water solutions in doses of 0.4 g/kg of body weight. The evaluation of the decontaminating effectiveness of the above DTPA compounds, taking into account veterinary-clinical and veterinary-sanitary aspects, was made with to the individual radioisotopes on the basis of radiometric studies. These studies carried out after 1,2,4,6,15 days from the contamination, by using a measurement system, concerned the following organs and tissues: blood, brain, heart, muscles of the thigh and arm, lungs, kidneys, liver, stomach, colon, bone, thyroid gland. The results expressing the per cent values of radioactivity of the organs in relation to the dose of the radioisotopes introduced into the organism and to the value of radioactivity of the particular organs in Bq/100 mg of ash, including discussion and conclusions, are presented in individual groups. From these data it can be assumed for practical veterinary purpose that Ca-, Zn-, MnDTPA chelates show an effective action with respect to the veterinary-clinical aspect in contamination with radiocerium, and with respect to the veterinary-sanitary aspect in contamination with radiocerium and radioiiodine; less effective action with respect to the veterinary-sanitary aspect, and ineffective with respect to the veterinary-clinical aspect in contamination with radiocesium; negative one with respect to both aspects in contamination with radiostrontium. As regards the individual chelating compounds, the most effective can be recognized sodium zinc salt of DTPA.

Animals↗

Comparison of a radioisotopic incorporation method and the mouse ear swelling test (MEST) for contact sensitivity to weak sensitizers.

A radioisotopic incorporation assay utilizing [125I]iododeoxyuridine was compared to the standard mouse ear swelling test (MEST) for the strong sensitizers dinitrofluorobenzene and oxazolone, and for the three weak sensitizers ethylenediamine (EDA), glutaraldehyde, and nickel sulfate. Mice were sensitized epicutaneously on the abdomen for 4 consecutive days prior to challenging the left ear with the test agent and the right ear with the vehicle. A comparison of the mean difference between the test and the control ears showed that measuring reactivity 48 hr postchallenge on Day 7 is the most sensitive time period in the radioisotopic incorporation method. Both the isotopic and MEST assays gave positive results with the potent sensitizers, although the response detected by isotopic labeling of emigrating cells was up to 1000-fold greater than that determined by ear swelling measurements. No response was detected to the moderate to weak sensitizer EDA in either assay. Reactivity to glutaraldehyde was not detected by the radioisotopic assay but was minimally responsive and significant by the MEST. The opposite was true for nickel sulfate where minimal but significant reactivity was seen in the isotopic assay but not in the MEST. Although the radioisotopic assay had the advantages of being more quantitative and of having improved sensitivity, it was of no greater value than the MEST for detecting weak sensitizers. It was concluded that the mouse was not a suitable model for routinely detecting reactivity to weak sensitizers regardless of which of the two assays were used.

Animals↗

Radioisotope stents for the prevention of restenosis: what did we learn from pre-clinical studies?

This article will discuss the lessons learned by using stents implanted with low activities of radioisotopes to prevent in-stent restenosis. A continuous low-dose rate radiation delivered by radioisotope stents has been shown to reduce the proliferative activity of smooth muscle cells and to inhibit neointimal growth. However, the radiation also delays endothelialization of the stents. Both the dose rate and the cumulative dose delivered by radioisotope stents appear to affect outcome. The neointima covering radioactive stents is characterized by a reduced cellularity, increased amounts of fibrin and extracellular matrix proteins. Aneurysm formation or excessive tissue destruction due to the radiation were not observed. Animals studies including up to 1 year follow-up periods suggest that beta-particle-radiation as well as gamma-radiation are effective in reducing neointimal hyperplasia. It is still unknown, however, which range of activities are needed and if a combination of radioisotopes, i.e. with short and long halflives, further reduce neotima formation over the long-term. An appropriate stent design for homogenous dose distribution around the stent may be important, i.e. articulations or large cell sizes may have disadvantages. Augmented neointima formation at the ends of radioactive stents, in particular when using beta-particle emitting stents, has been observed in animal models. Future studies will focus on the effects of increasing activity levels at the stent ends, optimal stent designs, alternative isotopes and different dosing strategies.

Journal Article↗

Dose estimate of exposure to radioisotopes in molecular and cellular biology.

A method for prospectively evaluating the annual equivalent doses and effective dose to biomedical researchers working with unsealed radioisotopes, and their classification, is presented here. Simplified formulae relate occupational data to a reasonable overestimate of the annual effective dose, and the equivalent doses to the hands and to the skin. The procedure, up to the classification of personnel and laboratories, can be made fully automatic, using a common spreadsheet on a personal computer. The method is based on occupational data, accounting for the amounts of each radioisotope used by a researcher, the time of exposure and the overall amounts employed in the laboratories where experiments are performed. The former data serve to forecast a contribution to the dose arising from a researcher's own work, the latter to a forecast of an 'environmental' contribution deriving simply from the presence in a laboratory where other people are working with radioisotopes. The estimates of the doses due to one's own radioisotope handling and to 'environment' were corrected for accidental exposure, considered as a linear function of the manipulated activity or of the time spent in the laboratories respectively, and summed up to give the effective dose. The effective dose associated with some common experiments in molecular and cellular biology is pre-evaluated by this method.

Biometry↗

Radioisotope-Guided Surgical Biopsy of Suspected Osseous Metastases.

BACKGROUND: Radioisotope bone scanning is frequently used to stage patients with suspected or proven malignancies. Since false-positive results are common, especially in the ribs, open biopsy is often necessary. The conventional approach of visual inspection of the bone scan image to guide the surgeon usually requires excision of a large area of one or two ribs to assure that the biopsy was performed on the correct rib. A more precise method to guide the biopsy is desirable. METHODS: One technique to localize the suspicious area of bone intraoperatively for accurate biopsy involves percutaneous injection of the bone abnormality with a radioisotope followed by injection of methylene blue into the periosteum and subsequent open surgical biopsy. A more recent technique uses a hand-held gamma probe in a sterile sleeve in the operating room to locate the bone "hot spot" directly in the wound to guide the biopsy. RESULTS: Both techniques are effective in pinpointing the bone scan abnormality, but use of the gamma probe is less cumbersome and consumes less time and fewer resources. In one series of 10 patients undergoing gamma probe-guided biopsies of 13 rib and 1 sternal bone scan lesions, this technique showed a sensitivity of 100% in locating the area of abnormal radioisotope uptake. All biopsies yielded an abnormal diagnosis to account for the bone scan abnormality, but only 4 of 14 (29%) demonstrated metastatic tumor. CONCLUSIONS: Techniques described for radioisotope-guided localization of areas of increased tracer uptake in asymptomatic suspected bone metastases are accurate, sensitive guides to the open biopsy of these bony abnormalities. Due to the high false-positive rates in these asymptomatic but suspicious bone scan abnormalities, a diagnosis should be histologically confirmed.

Journal Article↗