Non-radioactive Iodine Research Articles

Stability and toxicity of Clostridium perfringens type D epsilon prototoxin treated by iodine

Purified epsilon prototoxin of Clostridium perfringens type D was produced, purified, and detoxified by the stoiechiometric method of non-radioactive iodine incorporation. Different degrees of iodination were perfomed and the toxicity of the derivatives were analysed by in vivo studies. Toxicity decreased inversely to the iodine incorporation. Eletrophoretic analysis showed different levels of stability of samples kept under different temperatures 4ºC, - 20ºC, and -80 ºC. The iodinated prototoxins were stocked for a period of four months.

Quantification of iodine in porous hydroxyapatite matrices for application as radioactive sources in brachytherapy

In this study, non-radioactive iodine was incorporated in two types of biodegradable hydroxyapatite-based porous matrices (HA and HACL) through impregnation process from sodium iodine aqueous solutions with varying concentrations (0.5 and 1.0 mol/L) . The results revealed that both systems presented a high capacity of incorporating iodine into their matrices. The quantity of incorporated iodine was measured through Neutron Activation Analysis (NAA). The porous ceramic matrices based on hydroxyapatite demonstrated a great potential for uses in low dose rate (LDR) brachytherapy.

Preliminary quantitative analysis of myocardial fatty acid metabolism from fluorescent X-ray computed tomography imaging

Fluorescent X-ray computed tomography (FXCT) using synchrotron radiation reveals the cross-sectional distribution of specific elements in biomedical objects. The aim of this study was to investigate the feasibility of FXCT imaging to assess the myocardial metabolic state quantitatively. Hearts labelled with non-radioactive iodine myocardial fatty acid agent 15-p-(iodophenyl)-3-methylpentadecanoic acid (BMIPP) from cardiomyopathic and normal hamsters were imaged. FXCT images were compared with optical microscope images. Myocardial fatty acid metabolism enhanced with BMIPP was clearly depicted by FXCT, which showed an almost homogeneous image for normal and a heterogeneous image for cardiomyopathic hearts. Morphological structures of the heart such as the left ventricle and myocardial wall were also visualized by FXCT. Optical microscopy showed no fibrosis in normal and slight interstitial fibrosis in cardiomyopathic hearts. In the case of cardiomyopathy, the area of significantly reduced BMIPP uptake was 39% in the short axis of the mid-left ventricle in the FXCT image, whereas a slight interstitial fibrosis of around 12% was recognized by optical microscopy for the same slice. This result indicated that reduced BMIPP uptake was caused by the myocardial fatty acid metabolic abnormality, not by the fibrosis in cardiomyopathy. Thus, FXCT images might be used to assess the quantitative metabolic analysis in small animal models of heart diseases.

Imaging Therapeutic Proteins in Gelatin for Controlled Drug Release

AbstractPreliminary results from this study show that x‐ray microcomputed tomography can be used to image model proteins for bone inducing growth factors. Small quantities (<1 μg protein/mg gelatin) of soybean trypsin inhibitor labeled with either gold nanoparticles or nonradioactive iodine were detected using synchrotron radiation. These results could lead to a new method of measuring the release profile of therapeutic proteins.

Tratamento do carcinoma diferenciado da tireóide com iodo-131: intervenções para aumentar a dose absorvida de radiação

Our aim was to analyze measures taken to increase the radiation absorbed dose (DOSE) during treatment of well-differentiated thyroid cancer (DTC) with iodine-131. An increase in DOSE is achieved by: avoiding competition with non-radioactive iodine, stimulating cellular uptake/retention, increasing the administered activity. Basis and results of each one of these methods were reviewed. Although it is difficult to demonstrate an increase in survival, there is a direct relation between DOSE and tumoral response in DTC. Different approaches can be used aiming an increase in DOSE, with a possible improvement in tumoral response for treatment with iodine-131. Although DTC is a relatively benign disease, a better response to treatment is highly desirable in high-risk patients, who have few other options of therapy. An increase in DOSE during treatment of DTC can be achieved using the described interventions, which should be used in high-risk cases of DTC.

The suitability of iodinated Angiotensin-(1–7) peptides as pharmacological tools

Introduction: The heptapeptide Angiotensin-(1–7) [(Ang-(1–7)] is a biologically active component of the Renin–Angiotensin System. Pharmacological studies often involve Ang-(1–7) radioactively labelled with 125I. Given the small size of the original peptide, we investigated whether introduction of a rather bulky iodine label interferes with the biological activity of Ang-(1–7). Methods: Ang-(1–7) was labelled with nonradioactive iodine with the chloramine-T method. The reaction products were separated on HPLC and analysed with mass spectrometry. The products were tested for biological activity in two ways: The ability of labelled Ang-(1–7) to block Ang II-induced contraction in rat aortic rings was tested in an organ bath setup. The affinity of labelled angiotensin for ACE in rat plasma was examined in vitro. Results: Iodination of Angiotensin-(1–7) resulted in two main products: monoiodinated and diiodinated Ang-(1–7) that could be easily separated on HPLC. In an organ bath experiment, monoiodinated Ang-(1–7) blocked Ang II responses identical to the native compound, whereas diiodinated Ang-(1–7) had lost its ability to block Ang II responses. Likewise, monoiodinated Ang-(1–7) had retained its affinity for ACE, while the affinity of diiodinated Ang-(1–7) was greatly reduced. Discussion: Monoiodinated Ang-(1–7) has a biological activity identical to the native compound, whereas this is lost in diiodinated Ang-(1–7). Therefore, only the monoiodinated radioactive form seems suited for pharmacological studies.

Determination of choline and ethanolamine plasmalogens in human plasma by HPLC using radioactive triiodide (1-) ion (125I3−)

For the purpose of developing highly sensitive and convenient determination of plasmalogens, the high-performance liquid chromatography (HPLC) method using radioactive iodine ( 125 I) was investigated. Radioactive triiodide (1-) ion ( 125 I 3 − ), which is an actual iodine form capable of reacting with vinyl ether bond (–CH 2 –O–CH=CH–) of plasmalogens, could be safely and efficiently produced by oxidizing a commercial radioactive sodium iodine (Na 125 I) with hydrogen peroxide (H 2 O 2 ) under acid condition (pH 5.5–6.0), which is called iodine-125 reagent. I 3 − specifically reacted with plasmalogens at the molar ratio of 1:1 in methanol, and 1 or 2 mol of plasmalogens was involved in the binding with iodine per iodine atom, resulting in the formation of stable iodine-binding phospholipids. The HPLC system with Diol column and acetonitrile/water as a mobile phase was available for separating iodine-binding phospholipids from nonbinding free iodine and for separately eluting iodine-binding phospholipids derived from choline and ethanolamine plasmalogens. Using iodine-125 reagent (1.85 MBq/ml), plasmalogens were detectable at high sensitivity of 10,000–15,000 cpm/nmol, which is more than 1000-fold higher sensitivity than the classical determination with nonradioactive iodine. Plasmalogen concentrations in human plasma were measured with the HPLC system and determined as, on average, 129.1 ± 31.3 μM ( n =8) in a 1.2 content ratio of choline to ethanolamine plasmalogens, a concentration that nearly agrees with the value reported previously.

Determination of choline and ethanolamine plasmalogens in human plasma by HPLC using radioactive triiodide (1-) ion ( 125I 3−)

For the purpose of developing highly sensitive and convenient determination of plasmalogens, the high-performance liquid chromatography (HPLC) method using radioactive iodine ( 125I) was investigated. Radioactive triiodide (1-) ion ( 125I 3 −), which is an actual iodine form capable of reacting with vinyl ether bond (–CH 2–O–CH=CH–) of plasmalogens, could be safely and efficiently produced by oxidizing a commercial radioactive sodium iodine (Na 125I) with hydrogen peroxide (H 2O 2) under acid condition (pH 5.5–6.0), which is called iodine-125 reagent. I 3 − specifically reacted with plasmalogens at the molar ratio of 1:1 in methanol, and 1 or 2 mol of plasmalogens was involved in the binding with iodine per iodine atom, resulting in the formation of stable iodine-binding phospholipids. The HPLC system with Diol column and acetonitrile/water as a mobile phase was available for separating iodine-binding phospholipids from nonbinding free iodine and for separately eluting iodine-binding phospholipids derived from choline and ethanolamine plasmalogens. Using iodine-125 reagent (1.85 MBq/ml), plasmalogens were detectable at high sensitivity of 10,000–15,000 cpm/nmol, which is more than 1000-fold higher sensitivity than the classical determination with nonradioactive iodine. Plasmalogen concentrations in human plasma were measured with the HPLC system and determined as, on average, 129.1 ± 31.3 μM ( n=8) in a 1.2 content ratio of choline to ethanolamine plasmalogens, a concentration that nearly agrees with the value reported previously.

Low-iodine diet in the treatment of differentiated thyroid cancer with radioactive iodine.

It is eminently reasonable to exploit the properties of radioactive iodine for the treatment of thyroid cancer, which has a unique avidity for iodine. An LID that restricts nonradioactive iodine, 127I, is rational if it allows greater radioactive iodine localization and delivery of tumoricidal doses of radiation. As discussed, the increased turnover of iodine on an LID and decreased pool size in thyroid cancer may compromise this goal.

Characterization of a novel radiolabeled peptide selective for a subpopulation of voltage-gated potassium channels in mammalian brain.

BgK, a 37-amino acid voltage-gated potassium (Kv) 1 channel blocker isolated from the sea anemone Bunodosoma granulifera, can be modified at certain positions to alter its pharmacological profile (Alessandri-Haber, N., Lecoq, A., Gasparini, S., Grangier-Macmath, G., Jacquet, G., Harvey, A. L., de Medeiros, C., Rowan, E. G., Gola, M., Ménez, A., and Crest, M. (1999) J. Biol. Chem. 274, 35653-35661). In the present study, we report the design of two BgK analogs that have been radiolabeled with (125)INa. Whereas BgK(W5Y/Y26F) and its radiolabeled derivative, (125)I-BgK(W5Y/Y26F), bind to Kv1.1, Kv1.2, and Kv1.6 channels with potencies similar to those for the parent peptide, BgK, BgK(W5Y/F6A/Y26F) and its monoiodo-tyrosine derivative, (125)I-BgK(W5Y/F6A/Y26F), display a distinctive and unique pharmacological profile; they bind with high affinity to homomultimeric Kv1.1 and Kv1.6 channels, but not to Kv1.2 channels. Interaction of BgK(W5Y/F6A/Y26F) with potassium channels depends on the nature of a residue in the mouth of the channel, at a position that determines channel sensitivity to external tetraethylammonium. In native brain tissue, (125)I-BgK(W5Y/F6A/Y26F) binds to a population of Kv1 channels that appear to consist of at least two sensitive (Kv1.1 and/or Kv1.6) subunits, in adjacent position. Given its unique pharmacological properties, (125)I-BgK(W5Y/F6A/Y26F) represents a new tool for studying subpopulations of Kv1 channels in native tissues.

Plasma clearance of iodine contrast media as a measure of glomerular filtration rate in critically ill patients.

The selection of the optimal method for assessing renal function relies on the accuracy of the technique. Plasma clearance of nonradioactive iodine contrast media (i.e., iohexol or iopromide) has been suggested as a reliable alternative to the renal clearance of inulin for estimating glomerular filtration rate (GFR). The accuracy of this method when used with critically ill patients displaying different levels of renal function in an intensive care unit (ICU) has not, until now, been examined. The accuracy of double- and multiple-point iohexol or iopromide plasma clearances was compared with that of already established techniques for measuring GFR (creatinine clearance, formula clearance by Cockcroft and Gault) and with that of inulin clearance, which is regarded as the gold standard for the measurement of GFR. Values were obtained from 31 ICU patients who exhibited a wide range of renal function (serum creatinine: 0.6-6.7 mg/dL). Inulin clearance was performed using the constant-infusion technique. Creatinine clearance was determined from 24-hr urine samples. The clearance formula was calculated according to Cockcroft and Gault's formula. Iohexol or iopromide were applied as a single intravenous dose, and blood samples were taken up to 6 hrs after the injection. Iodine concentrations were determined by radiographic fluorescence. Plasma clearance of iohexol/iopromide measured after the single injection of contrast media and that of the conventional inulin clearance was almost identical (y = 0.971x + 7.65, r2 =.96; n = 31). Two-point clearance of iohexol/iopromide (double sampling technique) was as reliable as the three-point clearance (three-slope-intercept method, y = 0.995x + 0.62, r2 =.999; n = 18). With respect to inulin clearance, GFR measurements determined by creatinine clearance or according to the formula given by Cockcroft and Gault revealed errors that increased proportionally (y = 1.03x, r2 =.88; n = 27; and y = 0.93x, r2 =.62; n = 31, respectively). It could also be shown that the accuracy of GFR measurements involving plasma clearance of iohexol was not greatly affected by the degree of renal insufficiency or the route by which contrast media were applied. These findings indicate that the determination of plasma clearance of iohexol/iopromide is a simple, rapid, and accurate method that can indeed be used for estimating GFR in ICU patients with normal renal function or even different degrees of renal insufficiency.

Radioiodine and the treatment of hyperthyroidism: the early history.

Little was known about iodine metabolism in the mid-1930s, but when Saul Hertz and his chief, J. Howard Means, at the Massachusetts General Hospital (MGH) realized in 1936 that radioiodine could be made and used as a tracer, they arranged with physicists Robley Evans and Arthur Roberts at the Massachusetts Institute of Technology (MIT) to make the short-lived 128I and study its physiology in rabbits. By 1938, they showed that the rabbit's thyroid gland rapidly took up 128I, especially when there was only a little non-radioactive iodine present. There was, however, no hope of using 128I as a treatment because of its brief half-life (25 minutes). In 1939, Joseph Hamilton and Mayo Soley, working with Ernest Lawrence's cyclotron in Berkeley, California, were able to make several radioiodines; one was 130I (12-hour half-life) and another 131I (8-day half-life). They were the first to give these radioiodines to humans to study iodine physiology. The MGH-MIT group also built a cyclotron and by 1940 had generated these two new radioiodines. One of the goals of both groups was the treatment of hyperthyroidism. Hertz and Roberts were the first to do so on March 31, 1941; Hamilton and John Lawrence, Ernest's brother, began on October 12, 1941. By 1942, the United States was actively fighting in World War II. That year both Boston and Berkeley groups have preliminary data on the treatment of hyperthyroidism in Atlantic City; both showed that it was effective and went on to treat more patients. In Berkeley the therapy was viewed cautiously, and, in many case, the physicists were mainly occupied with work for the Manhattan District. In Boston Hertz used the therapy as often as he could, emphasizing the use of 130I, until he joined the U.S. Navy in 1943. Earle Chapman, a clinician on the voluntary staff of the MGH, took over Hertz's practice in 1943; their later differences over the precise treatment and who was in charge led to their falling out. After Hertz's release from the Navy he was not permitted to return to the MGH and became quite bitter; Chapman stayed on at the MGH. After the war was over, both had acquired a sufficient number of patients--there was then no such thing as a controlled trial--and wrote up the results for publication. Each wrote a different physicist, Hertz with Roberts and Chapman with Evans. When Hertz learned that Chapman's paper was being considered by the Journal of the American Medical Associations, he quickly sent his manuscript to JAMA as well. Although the editor of JAMA was puzzled by two papers on the same topic from the same institution, both papers appeared in the same issue of JAMA on May 11, 1964, and announced the new therapy was effective treatment for hyperthyroidism.

Specific determination of tyrosine-phosphorylated proteins and peptides by differential iodination

A new method for the selective and quantitative determination of phosphotyrosine residues is presented using a differential iodination technique. Characterization of tyrosine-phosphorylated proteins was performed in a biological system using human U937 myeloid leukemia cells. The method is based on the saturation of free iodine binding sites using non-radioactive iodine. Samples are then treated with alkaline phosphatase. New iodine binding sites in dephosphorylated tyrosines are subsequently radio-iodinated, resulting in specific labeling of tyrosine phosphates. Separation is performed by RP-HPLC or sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Radiolabeled proteins are then identified using a radioactivity detector or autoradiography.

Use of the Nonradioactive Iodine Label and the Avidinbiotin System for Immunoassays

Abstract The use of iodinated Bolton-Hunter reagent (IBHR) - labelled avidin and of IBHR-labelled biotin in immunoassays for the measurement of human IgG is investigated. The IBHR label is detected using the reaction between cerium(IV) and antimony(III). The results are compared to those obtained for immunoassays using IBHR-labelled antibodies or enzyme-labelled antibodies.

Nuclear Weapons Testing Fallout and Thyroid Disease

To the Editor. —In a recent article by Kerber et al 1 an attempt was made to study thyroid disease in relation to fallout from nuclear weapons testing. While such information would definitely be of interest, the reported study had little hope from the start of succeeding or achieving the authors' goals. The shortcomings of their methods cannot be made light of. Dietary histories obtained 22 years after the fact would cause one to scoff at the likelihood of an accurate depiction of radioiodine intake. The authors report a method for determining dose to the thyroid from iodine 131 ( 131 I) based on a largely untested modeling approach. The actual radiation dose to the thyroid in human beings has not been carefully examined in a group of subjects whose dietary history was collected as reported. The background radiation to the thyroid for the nonradioactive iodine—exposed population in Arizona leads to

LH-RH analogue carrying a cytotoxic radical is internalized by rat pituitary cells in vitro

The binding and internalization of a cytotoxic analogue of luteinizing hormone-releasing hormone (LH-RH), T-98 (agonist [ d-Lys 6]LH-RH linked to glutaryl-2-(hydroxymethyl)anthraquinone), by rat anterior pituitary cells was investigated. Analogue T-98 was bound to pituitary membrane binding sites for LH-RH with a high affinity ( K d =1.2 nM ) and was 17 times more potent in releasing luteinizing hormone (LH) from superfused rat pituitary cells than LH-RH. The labeling of this cytotoxic LH-RH analogue was carried out both with radioactive ( 125I) and nonradioactive iodine. Monoiodination of the Tyr 5 residue of T-98 did not significantly affect its binding affinity but greatly decreased its LH-releasing activity to about 3% of the original value. Di-iodination in the same position lowered binding affinity twenty-threefold and further diminished LH-releasing potency. [ 125I]T-98 was found to bind very strongly to polystyrene, which precluded the use of regular tissue culture plasticware in our experiments. In pituitary cells cultured in glass vials, binding and internalization of [ 125I]T-98 were observed, which were time and temperature dependent, and which could be inhibited by excess unlabeled analogue. No enzymatic degradation of labeled T-98 was detected in the culture medium during the incubation. Our results indicate that T-98 is internalized by pituitary gonadotropes through receptor-mediated endocytosis. Because this new class of compounds was designed as anticancer drugs, our findings also suggest that this cytotoxic LH-RH agonist may also be internalized by LH-RH receptors present in breast, prostate, ovarian, and other tumors.

The optimisation of a novel iodide microassay and its application in an immunoassay for human antibody levels in serum

Radioactive iodine has been used as an antibody label in many immunoassays. The feasibility of using non-radioactive iodine as a label was investigated. A microassay for iodide based on the Sandell-Kolthoff reaction was optimised. It was used to detect iodine-labelled antibody and successfully applied to the detection of human IgG in serum samples. The performance of this assay system compared with enzyme-linked immunosorbent assay using HRP was evaluated.

129I and 137Cs fission products in thyroids of animals, 1984-1991.

Iodine is intensely concentrated in the thyroid of animals, while 137Cs is not. In this study, 129I and 137Cs concentrations were determined in animal thyroids from selected areas during 1984-1991. The thyroids were from deer killed within the Savannah River Site (SRS) in South Carolina; from the environs of Oak Ridge (OR), Tennessee; West Tennessee; and Florida. Thyroids from sheep slaughtered routinely in Birmingham, England (UK), were also tested. The glands were analyzed by x-ray spectroscopy using a high-purity germanium well detector. 129I concentrations of 1 to 102 Bq 129I (g thyroid)-1 were found in 6.8% of deer thyroids from SRS. Eighty-nine percent of the thyroids from SRS and 38% of those from OR contained 129I concentrations of 0.01 to 1.0 Bq 129I g-1. No thyroids from West Tennessee or Florida had more than 4 mBq 129I g-1. Cesium was found to be distributed differently; 38% of the thyroids from SRS contained 0.1 to 0.65 Bq 137Cs g-1, and the highest concentrations appeared periodically, during November and December. Ten to 100 mBq of 137Cs were found in 60% of thyroids from SRS, 79% of those from Florida, 52% of those from OR, and 22% of those from West Tennessee. In thyroids from SRS and Florida, most of the 137Cs has been from worldwide fallout on sandy soil which permits 137Cs-rich vegetation; if a fraction of the 137Cs is from other sources, it has not been defined. The unique finding of this report is the high incidence and persistence of > 0.01 Bq 129I (g thyroid)-1 in deer from OR and SRS. 129I is a marker for fission products, but it is not a radiological hazard because of its very slow radioactive decay and its continual dilution by additions of nonradioactive iodine to the environment.

The role of functional imaging in neoplasms of the thyroid.

Iodine-123 and Iodine-131 have suitable physical properties that enable them to be used for functional imaging of the thyroid. Iodine-123 is used for routine testing for hyperthyroidism and thyroid nodules, whereas I-131, which has a longer half-life, is used for whole body imaging for detecting metastatic thyroid cancer in patients who have undergone thyroidectomy. The radionuclides of iodine are trapped and organified like nonradioactive iodine. In contrast, technetium as pertechnetate is trapped by the thyroid and can be used for imaging immediately after intravenous injection. There can be differences in scintiscans made in the same patient using radioiodine vs. technetium. Thallium is a useful adjuvant imaging agent for thyroid cancer. It should be stressed that correlation with the clinical findings and biochemical thyroid function tests are very important when evaluating thyroid scintiscans.

Development of a non-radioactive iodine label-based method for the determination of proteolytic activity

A method for the determination of proteolytic activity is described, based on the use of non-radioactive iodine-labelled bovine serum albumin (BSA) as the substrate for proteolytic activity. Iodinated BSA catalyses the Sandell–Kolthoff reaction, involving the oxidation of arsenic(III) by cerium(IV), and the degree of catalysis can be used to detect proteolytic activity. The assay is simple and sensitive, allowing the detection of 100 ng ml–1 of proteinase.