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Application of radioactive precursors for the evaluation of sensitivity of cancer cells to anticancer drugs.

An in vitro drug sensitivity test was developed to estimate the lethal effects of drugs on cancer cells. Cancer cells were incubated in the presence of radioactive precursors and anticancer drugs. The drug effects were estimated from the changes in rates of incorporation of precursors into DNA, RNA, and protein. A microtiter plate and a multiple automatic cell harvester made feasible handling of a large number of samples. Incorporation of radioactive precursors was well correlated with drug-induced cell lethality. The results of this test were also correlated with in vivo regression of tumors of mice. This test appeared to be more reliable than other similar tests of cell lethality in vitro. For utilization in clinical studies, a test plate was simplified and 25 human cancers were tested. The in vitro results demonstrated a positive correlation with clinical results in 80% of the observations.

Adult↗

Degradation of radioactively labelled protein in the small intestine of the suckling rat.

The absorption of 125I-labelled bovine IgG, after oral and intraluminal administration to young rats, has been followed by gel filtration and quantitatively by TCA precipitation. After intraluminal administration of the radioactive dose into the proximal small intestine most of the absorbed dose could be accounted for in a protein-bound form and the bulk of this radioactivity corresponded to native protein. Catabolism of the standard dose was far more efficient in the ileal regions of the small intestine, only 10% of the absorbed dose was transmitted as intact protein and large degradation products. Investigations on the attachment and release of labelled proteins from different sections of the small intestine of the young rat have also been recorded.

Administration, Oral↗

Radioactive 133-Xenon gas-filled balloon to prevent restenosis: dosimetry, efficacy, and safety considerations.

BACKGROUND: Ionizing radiation administered intraluminally via catheter-based systems using solid beta and gamma sources or liquid-filled balloons has shown reduction in the neointima formation after injury in the porcine model. We propose a novel system that uses a 133-Xenon (133Xe) radioactive gas-filled balloon catheter system. METHODS AND RESULTS: Overstretch balloon injury was performed in the coronary arteries of 33 domestic pigs. A novel 133Xe radioactive gas-filled balloon (3.5/45 mm) was positioned to overlap the injured segment with margins. After vacuum was obtained in the balloon catheter, approximately 2.5 cc of 133Xe gas was injected to fill the balloon. Doses of 0, 7.5, 15, and 30 Gy were delivered to a distance of 0.25 mm from the balloon surface. The dwell time ranged from 1.0 to 4.0 minutes, depending on the dose. Localization of 133Xe in the balloon was verified by a gamma camera. The average activity in a 3.5/45-mm balloon was measured at 67.7+/-12.1 mCi, and the total diffusion loss of the injected dose was 0.26% per minute of the injected dose. Bedside radiation exposure measured between 2 and 6 mR/h, and the shallow dose equivalent was calculated as 0.037 mrem per treatment. Histomorphometric analysis at 2 weeks showed inhibition of the intimal area (intimal area corrected for medial fracture length [IA/FL]) in the irradiated segments of 0.26+/-0.08 with 30 Gy, 0.07+/-0.24 with 15 Gy, and 0.12+/-0.89 with 7.5 Gy versus 0.76+/-0.08 with control P<0.001. CONCLUSIONS: 133Xe gas-filled balloon is feasible and effective in the reduction of neointima formation in the porcine model and safe for use in coronary arteries.

Angioplasty, Balloon, Coronary↗

Feasibility of radioactive embolization of intracranial aneurysms using 32P-implanted coils.

BACKGROUND AND PURPOSE: Beta radiation can prevent recanalization after embolization. Our goal was to assess the feasibility of endovascular treatment of intracranial aneurysms using coils of a predetermined activity of 32P per centimeter. METHODS: We studied the total length of coils deployed into 357 intracranial aneurysms. Aneurysmal volumes were estimated using 3 mathematical models. We simulated that coils were implanted with 0.26 microCi/cm of 32P, calculated resulting volumetric activities, and compared them with "effective" levels derived from experimental data and "safe" levels prescribed for the clinical use of 32P in cystic craniopharyngiomas. RESULTS: Effective activities would have been reached in 92% to 98% of lesions had the coils been radioactive at the time of treatment. CONCLUSIONS: Radioactive coil embolization of aneurysms is feasible in most patients.

Adult↗

Ventilation enhances pulmonary alveolar clearance of radioactive dipalmitoyl phosphatidylcholine in liposomes.

We examined the clearance from lungs of dipalmitoyl phosphatidylcholine (DPPC), the main component of pulmonary surfactant, after instillation in the form of radioactively labeled liposomes (small unilamellar vesicles) in anesthetized rabbits breathing spontaneously. There were 2 protocols: normal ventilation in control animals, and ventilation increased 100% by augmentation of the dead space in experimental animals. Liposomes containing 20% phosphatidylglycerol were also tested in animals breathing normally. We examined the stereospecificity of clearance with levo 14C-DPPC and dextro 3H-DPPC isomers. We measured phospholipid content and plotted curves of radioactivity versus time (0 to 5 h) for alveolar material obtained by lavage and for the whole lung. In the control animals (n = 15), alveolar clearance of 14C-L-DPPC was 7.8%/h, and with increased ventilation (n =13) it was 13.3%/h (p less than 0.025). With phosphatidylglycerol (n = 9) alveolar clearance during normal breathing was 13.9%/h(p less than 0.001). Alveolar clearance rates of 14C-L-DPPC and 3H-D-DPPC were not significantly different. Clearance from the whole lung did not differ between control and experimental animals or between isomers, and it averaged 3.1%/h.

Animals↗

The measure in vivo of regional cerebral oxygen utilization by means of oxyhemoglobin labeled with radioactive oxygen-15.

Regional cerebral oxygen utilization rate is measured in vivo by the following method:A small volume of blood with radioactive oxygen-15-tagged hemoglobin is rapidly injected into the internal carotid artery of the patient under study. The first injection is followed by the injection carried out under identical circumstances but with blood labeled with water-(15)O. After each injection, the distribution of the radioactive label in the brain is measured and recorded, as a function of time, by six collimated scintillation probes placed over the subject's head. The recording, subsequent to the first injection, reflects (a) the arrival of the labeled oxygen into the tissues, (b) its partial conversion into water of metabolism, and (c) the washout of labeled water from the brain. The ratio of the amount of labeled water formed to the amount of oxygen perfusing the tissues, which can be derived from the recording, is a measure of fractional oxygen utilization. The second injection provides a measure of blood flow by the interpretation of the washout of labeled water from brain tissues. The product, fractional oxygen utilization x blood flow x arterial oxygen content, gives a measure of oxygen utilization rate. Some aspects of the validity of this method are tested by the injection of a nondiffusible indicator, carboxyhemoglobin-(15)O. Regional cerebral oxygen utilization rates for a series of patients with cerebral pathology are reported.

Arteries↗

Sensitive and quantitative co-detection of two mRNA species by double radioactive in situ hybridization.

A better understanding of biological phenomena involving modulations of gene expression requires quantitative analysis of the expression of several genes in the same structure. For this purpose, we have developed a novel in situ hybridization method to quantify two different mRNA species in the same tissue section simultaneously. Two probes labeled with radioelements of significantly different energies ((3)H and (33)P or (35)S) were used to detect the mRNA species. Radioactive images corresponding to the detected mRNA species were acquired with a Micro Imager, a real-time, high-resolution digital autoradiography system. An algorithm was used to process the data such that the initial radioactive image acquired was filtered into two subimages, each representative of the hybridization result specific to one probe. This novel method allows local discrimination and quantification of the respective contributions of each label to each pixel and can therefore be used for quantitative analysis of two mRNAs with a resolution of 15-20 microm.

Algorithms↗

Detection of thymic surface antigens and radioactive labeling of mouse lymphoid cells.

A method for the permanent and simultaneous detection of tissue-specific surface antigens and internal radioactive labeling of mouse lymphoid cells is described. Target cells were first reacted with a mouse-derived "antithymocyte serum", incubated with peroxidase-conjugated rabbit serum against mouse immunoglobulins and placed in a substrate solution that leads to staining of the antigen-positive cells. Radioactive labeling was demonstrated by autoradiography performed after the antigen assay. More than 90% of antigen-positive thymocytes could be specifically stained in the assay without staining of similarly treated antigen-negative cells. Autoradiographic grains could be detected over both antigen-positive and antigen-negative cells.

Animals↗

Non-radioactive localization of substance P binding sites in rat brain and spinal cord using peptides labeled with 1.4-nm gold particles.

We present here a new method for non-radioactive labeling of substance P (SP) to demonstrate the distribution of its binding sites in histological sections. The peptide was labeled at the primary amino group with a 1.4-nm gold particle. In Western blots of membrane fractions of rat spinal cord, specific binding occurred at 38 and 58 KD. This binding was competitively suppressed by adding the native peptide. In addition, the SP-gold conjugate was able to displace the corresponding 125I-labeled peptide from binding proteins. In histological sections, binding sites could be shown in various parts of rat brain and spinal cord. The distribution patterns were comparable to those found in studies using autoradiographic methods. Adding the native peptide or a neurokinin 1 receptor agonist markedly reduced labeling of the tissue, whereas only a slight reduction was obtained after adding neurokinin A. Therefore, SP could be specifically labeled with a 1.4-nm gold particle to demonstrate its binding sites. This new method combines the advantages of receptor-ligand affinity binding with a non-radioactive detection system. It can be used for labeling peptides in general and therefore offers an alternative or addition to other methods used in study of the distribution of membrane receptors.

Animals↗

Use of adjunctive potassium iodide after radioactive iodine (131I) treatment of Graves' hyperthyroidism.

One hundred and nineteen patients with Graves' hyperthyroidism who were treated with 131I alone or 131I followed by potassium iodide (131I + KI) were studied retrospectively. Patients in both groups who required only a single dose of 131I for successful treatment of hyperthyroidism had similar age, gland size, 24-h radioactive iodine uptake, pretreatment serum T4 concentrations, and radioactive iodine treatment dose. Seven weeks after 131I, mean serum T4 concentrations were 12.3 +/- 6.1 micrograms/dl (mean +/- SD) in patients who received 131I alone and 8.0 +/- 3.9 micrograms/dl in patients who received 131I + KI (p less than 0.001). Sixty percent of the patients who received 131I + KI and remained euthyroid 1 yr after 131I treatment developed documented transient hypothyroidism while receiving KI (serum T4, 1.4 +/- 0.9 micrograms/dl). Patients with transient hypothyroidism receiving KI had larger estimated thyroid gland weights when hypothyroid than patients whose hypothyroidism was permanent (32 +/- 6 vs. 16 +/- 11 g; P less than 0.001). The overall incidence of hypothyroidism 1 yr after treatment with 131I was 58% in each of the two groups. Sixteen percent of each group were not successfully treated by a single dose of 131I and required further therapy. Adjunctive KI effectively treated thyrotoxicosis more rapidly than 131I alone without adversely affecting outcome at 1 yr; however, patients taking KI more often develop transient hypothyroidism.

Adult↗

Dose-dependent uptake of radioactivity by liver parenchymal and non-parenchymal cells after intravenous administration of fractionated 3H-heparin to rats.

The dose-dependent uptake of fractionated 3H-heparin in the subpopulations of liver cells, parenchymal and non-parenchymal cells, was characterized in rats in vivo. Following the intravenous administration of fractionated 3H-heparin, the radioactivity in plasma was eliminated according to the first order kinetics at each dose. However, the elimination rate constant decreased with dose over the dose range of 0.3 to 100 U/kg, suggesting nonlinear elimination. In accordance with the delay in the plasma elimination, the uptake rate constant of radioactivity by parenchymal as well as non-parenchymal cells of liver, the major distribution organ, also decreased. Although heparin has long been considered to be taken up by a reticuloendothelial system (RES) such as non-parenchymal cells in the liver, the uptake of fractionated 3H-heparin by parenchymal cells was found to be comparable with that by non-parenchymal cells at the lowest dose of 0.3 U/kg, and even larger than that by non-parenchymal cells at the highest dose of 100 U/kg. The uptake clearances of fractionated 3H-heparin at the dose of 0.3 U/kg were 86.4 and 504 ml/10(8) cells/d, respectively, for parenchymal and non-parenchymal cells. These values were much larger than those reported for polyvinylpyrrolidone, which has been suggested to be taken up by fluid phase endocytosis. Thus, the present study revealed the significant contribution of parenchymal cells in the hepatic uptake of fractionated 3H-heparin. The dose-dependent uptake with high clearance values in both parenchymal and non-parenchymal cells provides an in vivo suggestion of the specialized transport of fractionated heparin in these two subpopulations of liver cells.

Animals↗

Ga-labeling of immunoglobulin G with high specific radioactivity.

To obtain radiogallium labeled immunoglobulin G with a high specific radioactivity for in vitro use, a 67Ga source was purified by extraction from 67Ga-gallium citrate with butyl acetate, and a 67Ga-labeling solution was produced. This solution was then used to label a deferoxamine-immunoglobulin G conjugate. Both a very high specific radioactivity (872 +/- 56 MBq/mg) and a high labeling efficiency (94.0%) were achieved.

Gallium Radioisotopes↗

The effects of radioactive iodine in thyroid remnant ablation and treatment of well differentiated thyroid carcinoma.

Although the use of radioactive iodine (131I) in the treatment of thyroid cancer is well established, treatment dose is not well standardized. In order to deduce the appropriate dose for thyroid remnant ablation and the effect of 131I in the treatment of distant metastases, data for 544 patients with papillary or follicular thyroid cancer were retrospectively reviewed. All patients received surgical treatment followed by post-operative 131I. If remnants were present in the 0.2 GBq 131I diagnostic scan, 1.1-3.7 GBq 131I were administered for ablation. For the treatment of distant metastases 3.7-5.6 GBq were used. Of 318 patients receiving 131I for thyroid remnant ablation, 290 were successfully ablated. After one dose of 1.1 GBq 131I, 82% (159/194) of thyroid remnants were ablated. During the follow-up period, two of 14 Stage IV patients with lung or mediastinal metastases at the time of operation achieved complete clinical remission. Factors identified as influencing response to 131I therapy included age, clinical stage, survival, recurrence, extent of surgery and the 1 month post-operative serum thyroglobulin (Tg) level. In conclusion 1.1 GBq 131I was adequate for thyroid remnant ablation unless distant metastases were present. Radioactive 131I has a role in the treatment of well differentiated thyroid carcinoma with pulmonary metastases but seems to be less effective for treatment of bone metastases.

Adenocarcinoma, Follicular↗

Radioactivity in books printed in Japan: its source and relation to the year of issue.

The radioactivities of the naturally occurring radionuclides (226Ra, 228Ra, 228Th and 40K) and a fallout nuclide (137Cs) in books produced in Japan in the 20th century were measured by gamma-ray spectrometry to obtain information on radiation emitted from books. The respective concentration ranges of 226Ra, 228Ra, 228Th, 40K, and 137Cs were 0.2-6.4, 0.4-11.2, 0.3-11.3, 1-112, and 0-3 Bq kg-1. X-ray diffraction spectra of the papers used in book printing showed that pyrophyllite, talc, kaolinite, and calcium carbonate were contained as fillers. A comparison of the radioactivity contents of the pulp and filler indicated that most of 226Ra, 228Ra, and 228Th in the books was present in the filler whereas 137Cs was in the pulp. The pattern of the concentration of each nuclide vs. the year of issue of the book was investigated. Patterns for the naturally occurring radionuclides were similar and were explained by the kinds of filler used. The pattern for 137Cs differed from the patterns of the naturally occurring radionuclides, having a marked peak in the mid-1960s.

Books↗

[Regional myocardial blood flow measurement with radioactive microspheres in dogs with myocardial ischemia].

In order to evaluate the radioactive microsphere technique used in our laboratory for measuring regional myocardial blood flow (RMBF) in dogs with myocardial ischemia, simultaneous blood flow measurements with three different nuclide (141Ce, 51Cr or 113Sn)-labeled microspheres were performed after coronary artery occlusion. There were excellent correlations between all paired RMBF values in 80 samples. The linear regression lines were expressed as: 51Cr = 1.09x 141Ce-0.02 (r = 0.996, SEE = 0.06); 113Sn = 0.99x 141Ce + 0.01 (r = 0.997, SEE = 0.05); 113Sn = 0.90x 51Cr + 0.03 (r = 0.991, SEE = 0.08). The duplicate variability ranged from 5.5 +/- 0.7 to 9.9 +/- 1.1%. When RMBF was measured before and after intravenous administration of nipradilol (0.2 mg/kg), a new beta-blocker, in a dog with myocardial ischemia, RMBF fell in the normal zone (23.6 +/- 1.6%), and did not change in the severely ischemic zone. Thus, this study demonstrated that RMBF can be measured accurately and repeatedly with radioactive microspheres in dogs with regional myocardial ischemia.

Adrenergic beta-Antagonists↗

Radioactive suture in the treatment of head an neck cancer.

I-125 seeds in Vicryl suture have been used as a radioactive suture in 24 cases of advanced malignancy of the head and neck. Twelve cases had metastatic carcinoma attached to the internal or common carotid artery. The goal was to excise surgically as much tumor as possible, then implant any residual tumor with this radioactive suture which remains as a permanent implant (half-life of 60 days). This preliminary study shows that use of I-125 impregnated Vicryl suture in this manner appears to produce improved long-term palliation and may increase local cure rates.

Follow-Up Studies↗

Biosorption of radioactive thorium by Sargassum filipendula.

In the present work, the biosorption of radioactive thorium was investigated using a dry biomass of Sargassum filipendula as the biosorbent material. Radioactive solutions containing between 2.0 and 500.0 microg thorium were tested by biosorption with S. filipendula, yielding uptake capacities from 20 to 100%, depending on the concentration of the solution. Kinetic studies indicated that equilibrium between the thorium solution and the solid fraction was achieved after three hours of contact and that a second-order model could express the equilibrium kinetics. In order to investigate the maximum biosorption capacity of the biomass an isotherm was done, based on the experimental data, which revealed the maximum uptake capacity to be 2.59 micromol thorium/g biomass. The experimental data fitted well to a Langmuir model, which provided a good correlation between the experimental and predicted thorium uptake values.

Absorption↗