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Thesis (PhD)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: A study was undertaken to investigate the radiochemical stability of the βiodoethoxyl moiety, a relatively novel prosthetic group employed in radiopharmaceutical chemistry, in which an oxygen atom in a β-position relative to the radioiodine atom has a stabilising effect on the aliphatic carbon-iodine bond. The investigation was started as a pilot study by synthesising various model compounds containing a β-radioiodoethoxyl moiety, as well as two reference compounds lacking such a moiety. The purpose was to determine the influence of various groups in the vicinity of the β-oxygen atom on the stability of the abovementioned moiety. Radiochemical stability tests were carried out in vitro at 37°C in human blood serum. The results confirmed the superior stability of such a moiety compared to that of the reference compounds and also showed that the branching of such an aliphatic unit resulted in a considerable improvement in its stability, especially over a longer period. The investigation was extended to the synthesis of other compounds containing a few selected β-iodoethoxyl moieties that showed improved stability in the pilot study work. Reference compounds containing the classical iodovinyl unit, as well as those lacking a stabilising β- oxygen atom, were also prepared. The carrier molecules used in this part of the work was a benzamide containing a phenolic oxygen atom which acted as the β-oxygen atom, as well as two heterocyclic amines, benzotriazole and 2-methyl-5-nitroimidazole, in which the β- iodoethoxyl moiety was linked to a secondary nitrogen atom. Various suitable alkylating agents were prepared, chemically linked to the carrier molecules, the resulting intermediate compounds converted into tosylate or triflate iodination precursors and labelled with radioiodine by means of iodide-for-tosylate/triflate exchange. In vitro stability tests of these compounds showed similar trends to those obtained with the model compounds. Moreover, the stability of the stabilised β-iodoethoxyl moiety compared favourably with that of the iodovinyl unit, especially when incorporated into a heterocyclic amine. The results of this study have shown that some of the radioiodinated compounds synthesized in this work, especially the nitroimidazole derivatives, have the potential to be considered as novel radiopharmaceuticals. / AFRIKAANSE OPSOMMING: 'n Studie is onderneem om die radiochemiese stabiliteit van die β-jodium-etoksi-eenheid te ondersoek. Dié eenheid is 'n relatief nuwe prostetiese groep wat in radiofarmaseutiese chemie gebruik word. Die suurstofatoom wat in 'n β-posisie relatief tot die radiojodiumatoom voorkom, oefen 'n stabiliserende invloed op die alifatiese koolstof-jodiumbinding uit. Die ondersoek het met 'n loodsstudie begin deur verskillende modelverbindings te sintetiseer wat 'n β-radiojodium-etoksi-eenheid bevat, asook twee verwysingsverbindings waarin so 'n eenheid ontbreek. Die doel hiermee was om die invloed van verskillende groepe, wat in die omgewing van die β-suurstofatoom voorkom, op die stabiliteit van die eenheid te bepaal. Radiochemiese stabiliteitstoetse is uitgevoer deur middel van inkubering in menslike bloedserum by 37°C. Die resultate het die groter stabiliteit van so 'n eenheid in vergelyking met dié van die verwysingsverbindings aangetoon, en het ook uitgewys dat vertakking van so 'n alifatiese eenheid 'n aansienlike verbetering in die stabiliteit tot gevolg gehad het, veraloor 'n langer periode. Die ondersoek is vervolgens uitgebrei deur verdere verbindings te sintetiseer wat beskik oor bepaalde uitgesoekte β-jodium-etoksi-eenhede, wat verbeterde stabiliteit in die loodsstudie getoon het. Verwysingsverbindings wat die klassieke jodiumvinieleenheid bevat het, sowel as dié waarin 'n stabiliserende β-suurstofatoom ontbreek het, is ook berei. Die draermolekules wat in hierdie deel van die studie gebruik is, was 'n bensamied met 'n fenoliese suurstofatoom wat as die β-suurstofatoom gedien het, sowel as twee heterosikliese amiene, bensotriasool en 2- metiel-5-nitroimidasool, waarin die β-jodium-etoksi-eenheid aan 'n sekondêre stikstofatoom geheg is. Verskillende geskikte alkileermiddels is berei, aan die draermolekules geheg, die tussenprodukte omskep in tosilate of triflate en met radiojodium gemerk deur middel van jodium-vir-tosilaatltriflaat-uitruiling. Stabiliteitstoetse van hierdie verbindings in bloedserum het soortgelyke tendense as dié van die aanvanklike modelverbindings getoon. Daarbenewens het die stabiliteit van die gestabiliseerde β-jodium-etoksi-eenheid gunstig vergelyk met dié van die jodiumviniel-eenheid, veral wanneer dit deel gevorm het van 'n heterosikliese amien. Die resultate van die studie het getoon dat sommige van die radiogejodeerde verbindings wat berei is, veral die nitroimidasoolderivate, die potensiaal het om as nuwe radiofarmaseutiese verbindings gebruik te kan word.

No description available.

Objective : An audit of the use and outcomes of Radioactive Iodine (RAI) therapy in the definitive management of thyrotoxicosis at Inkosi Albert Luthuli Central Hospital (IALCH), KwaZulu-Natal, South Africa. Methods : The clinical records of all new patients with thyrotoxicosis, referred in a 4 year period between 01/01/2003 and 31/12/2006, were analysed. Response to RAI was monitored using biochemical parameters (namely, Thyroid Stimulating Hormone and Free T4 levels). Rates of euthyroidism (cure), hypothyroidism and hyperthyroidism (treatment failure) were correlated to dose of RAI. Patients were followed-up for at least 2 years or until the onset of hypothyroidism. The follow-up period was until 31/12/2007. Results : One hundred and fourteen patients (37.7%), of a cohort of 302 new thyrotoxic patients treated with RAI, met the inclusion criteria. Ninety-six patients (84.2%) had Graves Disease (GD) whilst 18 had Toxic Nodular Disease (TND). At 2 year follow-up, 91 patients (79.8%) were hypothyroid, 10 (8.8%) were euthyroid and 13 (11.4%) were hyperthyroid. The average dose of RAI to achieve euthyroidism was 10mCi and hypothyroidism, 9.7mCi. The average time to achieve euthyroidism was 5.9 months and 10.1 months to become hypothyroid. Thirty-one patients (27.2%) remained persistently hyperthyroid after one dose of RAI. Patients with GD (88.5%) were more likely to become hypothyroid (p < 0.001) whilst 38.9% of TND patients remained hyperthyroid (p = .001). Baseline TFT values were significant in terms of outcomes correlated with the prescribed RAI dose i.e Low Dose (<8mCi) vs. Intermediate Dose (8-9mCi) vs. High Dose (>9mCi)(TSH p = 0.05; FT4 p = 0.003; FT3 p = 0.001). Conclusion : The majority of patients became hypothyroid over time, in keeping with reported data. In the public health sector, where early access to RAI (in terms of waiting times for appointments for RAI) and follow-up are major problems, early cure is essential to minimize the morbidity of thyrotoxicosis and this may be achieved with an initial high dose of RAI. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2011.

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Typescript (photocopy). / Digitized by Kansas Correctional Industries

This thesis concerned with iodine status, sources in human body, and measurements especially here in Canada, where iodine status for the Canadian population is not well known. With the recent re-emergence of iodine deficiency among individuals in other industrial countries, understanding the main sources of iodine to the Canadian population is necessary to ensure fortification strategies are justified and effective. Uncertinaty has arisen to the importance of iodized salt recently, along with medical warnings to reduce salt consumbtion. This conflicts give rise to improve scientific research and hone thier methods with new applications. The research question here is that: Can we benefit from the existence of long-lived radioiodine-129 in the environment and explore its potential as a tracer? To answer this question, the study was divided into an introductory chapter contains a review about the topic, then three research chapters. The second chapter was devoted to study the possibility of extracting 129I from human urine. As for third chapter of the thesis, it was about refining a method that already established, and use it to extract 129I from breastmilk using combustion, then determine the radiological dose of 129I in infants’ thyroid. While the fourth chapter was devoted to investigate the main sources of 127I and 129I in the Canadian diet based on daily food consumption and modelling the urinary iodine concentration for adults and infants through the novel application of a well-established compartment model implemented in AMBER. The path of this thesis was crowned with a set of results, which are detailed in the end of each chapter as follow: 1- The advantage of accelerator mass spectrometry (AMS) helps to measure 129I in human urine for the first time. The result for 25 participants from Ottawa ranged from 3.3 x 106 atoms/L to 884 x 106 atoms/L with a median of 108.7 x 106 atoms/L, and the 129I/127I ratio ranged from 7.38 x 10-12 to 3.97 x 10-10 with a mean of 1.3 x 10-10. 2- The concentration of 127I and 129I in Ottawa urine samples were significantly correlated and generally similar to the 129I concentrations and 129I/127I ratios from environmental samples collected around Ottawa. 3- This correlation suggests that 129I could be a potential nutritional tracer of dietary iodine. 4- In chapter 3, the 129I in breastmilk ranged from 1.26x108 atoms/L to 6.64x108 atoms/L with a median of 2.10 x108 atoms/L, and the 129I/127I ratio ranged from 1.27x10-10 to 9.9x10-10 with a median of 2.13x10-10. 5- A correlation was also observed between 127I and 129I concentrations in breastmilk. 6- The isotopic ratios in breastmilk were similar to Canadian cow’s’ milk, indicating that the milk of both cows and humans is a reflection of the 129I concentration of their local environment and the food ingested. 7- Result from chapter 3 confirms that humans are exposed to the 129I from birth through their mother breastmilk, giving them an average dose of 1.10 x10-4 Bq/year and thyroid dose rate equal to 5.92 x10-10 Sv/year. 8- In fourth chapter, the daily milk consumption was measured for 78 mother-infants’ pairs, and ranged from 275 -1202 g/day, with a mean of 731 g/day. This value agrees well with global infant milk intake which estimated at 730g/day. 9- The daily iodine intake from breastmilk ranged from 11.2 µg/day to 476.2 µg/day with a median of 127.9 µg/day. 10- The urinary iodine concentrations were estimated without urine collection using iodine biokinetic model, giving a median urinary iodine concentration (n=78) at 304.7 µg/L. The result was compared to those measured by Health Canada (median= 398.7 µg/L), showing a moderate correlation (r= 0.496). 11- A further comparison of the results was made based on gender shows that the difference between UIC in male and female infants measured by Health Canada and those estimated by AMBER is non-significant. 12- Through AMBER software, the influence of seven common diets on UICs was assessed to determine which foods play an important role in ensuring iodine adequacy. We observed that the main source of iodine in a vegan diet is grain products providing up to 70%, while in remaining diets the main source of iodine was dairy products (50-69%) when they are consumed. 13- The contribution of iodized salt to all Canadian diets was ranked second, after dairy, unless the diet is vegan or ovo-vegetarian, where dairy is not consumed, iodized salt was ranked first. 14- Among 23 scenarios for seven different diets, the urinary iodine-129 concentrations ranged from 1.4 x10-7 to 3.3 x10-7 µg/L with a median of 3.1 x10-7 µg/L, and the isotopic 129I/127I ratio ranged from 1.1 x10-9 to 1.2 x10-8 with a median of 2.8 x10-9. 15- In contrast to stable iodine, the highest isotopic ratio was observed in vegan diet, while the lowest was observed in ketogenic diet. This suggests that grain products are the main contributor of 129I to humans. 16- Despite being the primary contributors of stable iodine (127I), salt and dairy show a lower contribution of 129I. Based on this we can qualitatively predict the source of iodine 127 using isotopic ratio 129I/127I. For example, in cases where the isotopic ratio was between 10-8 and 10-9, therefore, the main sources of iodine in this person may be from grains products, vegetables, and fruits; and in cases where the isotopic ratio was between 10-10 and 10-11, therefore, the main sources of iodine in this person may be from dairy products and some contribution from salt. This study has shown the capability of 129I to be used in biomedical fields. In this thesis 129I used as a nutritional tracer where it helps to detect the sources of stable iodine in human body based on isotopic ratio. The extraction method invented in Chapter 2 can be used to evaluate 129I exposure directly in the human body for those who live nearby nuclear fuel reprocessing plants. An additional application for this method can be in assessing 129I in human to investigate 131I uptake in the event of a nuclear emergency using 129I in urine as a proxy. Moreover, the extraction technique used Chapter 3, can be extended to other biological samples such as thyroid or brain. Furthermore, Chapter 4 shows that with the right estimation of daily iodine intake and urine volume, a biokinetic model of iodine, built in the AMBER software, can predict urinary iodine concentration with a high degree of accuracy without collecting urine samples.

Thesis (MSc (Medical Imaging and Clinical Oncology. Nuclear Medicine))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: Radioiodine therapy is reputed to yield poorer results in male patients than in females. We retrospectively reviewed the records of 308 patients treated with radioiodine-131 (RAI) for Graves’ disease (n=266, 86.4%), toxic multinodular goitres (n=35, 11.4%) and toxic solitary nodules (n=7, 2.3%). The mean age of the men was 44 ±13.6 years (range 14-77 years). Patients with GD were predominantly in the younger age groups, while those with toxic nodular goitres were in the older range. Two hundred and fifty-nine patients (84.1%) were treated with a single dose of RAI, while 49 (15.9%) required further doses. A second dose had to be administered to 38 patients, while 8 received 3 doses, 2 got 4 doses and 1 patient had 5 doses in all (these included a first dose received prior to referral to our Thyroid Clinic). Cure was determined as euthyroidism or hypothyroidism at the 3-month follow-up visit. The average pre-treatment T4 value was 68.9 ± 31.8 pmol/L (range 5.7 – 155 pmol/L); while the mean Tc-99m pertechnetate uptake value was 15.8 ± 10.9% (range 0.88 - 62.9). Patients with GD presented with more severe hyperthyroidism than the other patients; mean free T4 of 71.9 ± 31.1 pmol/L compared to 51.4 ± 29.9 pmol/L for the TMG group of patients, and 39.6 ± 26.8 pmol/L for the TSN group (ANOVA p<0.0001, confirmed by the Kruskal-Wallis test). Patients with TMG and TSN were treated with higher doses than patients with GD; mean first doses of 349.3 ± 88.5 MBq and 428.1 ± 28.6 MBq respectively, compared to a mean dose of 325.1 ± 69.3 MBq for patients with GD. Treatment with multiple doses of RAI correlated with higher values of T4 and T3 at presentation (p<0.0001). However, none of the baseline variables of age, T4 and T3, and first dose of RAI was significant predictors of free T4 outcome at 3 months. A consistently higher dose was administered to the male patients, compared to female patients of similar age, diagnosis and level of thyrotoxicosis (Tc-99m pertechnetate uptake). Despite this, male patients had similar outcomes as the female patients 3 months after therapy. Our findings lend weight to the theory that male patients are more difficult to treat than their female counterparts, seeing that the former had similar outcomes despite the significantly higher doses of RAI administered to the males. / AFRIKAANSE OPSOMMING: Radiojodium terapie lewer na bewering swakker resultate in mans as in vroulike pasiënte. Die inligting van 308 pasiënte met Grave se siekte (n=266, 86.4%), toksiese multinodulêre tiroïed (n=35, 11.4%) en enkel toksiese nodules (n=7, 2.3%) wat met radiojodium (I-131) behandel is, is retrospektief nagegaan. Die gemiddelde ouderdom van die mans was 44 ±13.6 jaar (reikwydte 14-77 jaar). Die meeste pasiënte met Grave se siekte was in die jonger ouderdomsgroep, terwyl dié met toksiese multinodulêre tiroïed, ouer was. Tweehonderd nege-en-vyftig pasiënte (84.1%) is met ‘n enkel dosis radiojodium behandel, terwyl 49 (15.9%) meer as een dosis benodig het. ‘n Tweede dosis is aan 38 pasiënte gegee, terwyl agt 3 dosisse, twee 4 dosisse en 1 pasiënt 5 dosisse in totaal ontvang het (wat ‘n eerste dosis voor verwysing na die tiroïedkliniek, ingesluit het). Herstel is gedefinieer as eutiroïdisme of hipotiroidisme tydens die drie maande opvolgbesoek. Die gemiddelde T4-waarde voor behandeling was 68.9 ± 31.8 pmol/L (reikwydte 5.7–155 pmol/L); terwyl die gemiddelde Tc-99m pertegnetaatopname 15.8 ± 10.9% (reikwydte 0.88–62.9) was. Pasiënte met Grave se siekte het met erger hipertiroidisme as die ander pasiënte gepresenteer; met ‘n gemiddelde vry T4 van 71.9 ± 31.1 pmol/L vergeleke met 51.4 ± 29.9 pmol/L vir die toksiese multinodulêre tiroïedgroep en 39.6 ± 26.8 pmol/L vir die enkel toksiese nodule groep (ANOVA p<0.0001, bevestig met die Kruskal-Wallistoets). Pasiënte met toksiese multinodulêre tiroïed en enkel toksiese nodule, is met hoër dosisse as dié met Grave se siekte behandel; met ‘n gemiddelde eerste dosis van 349.3 ± 88.5 MBq en 428.1 ± 28.6 MBq onderskeidelik, vergeleke met ‘n gemiddelde dosis van 325.1 ± 69.3 MBq vir pasiënte met Grave se siekte. Behandeling met meer as een dosis radiojodium het gekorreleer met hoër T4- en T3- waardes by (p<0.0001). Geen van die basislyn veranderlikes (ouderdom, T4 en T3, en die eerste dosis radiojodium) was egter ‘n betekenisvolle voorspeller van die vry T4 uitkoms op 3 maande nie. Die dosis wat aan manlike pasiënte toegedien is, was konstant hoër, vergeleke met die vroulike pasiënte van dieselfde ouderdom, diagnose en vlak van tirotoksikose. (Tc-99m pertegnetaatopname). Ongeag hiervan, was die uitkoms by manlike en vroulike pasiënte 3 maande na terapie dieselfde. Ons bevindinge dra by tot die teorie dat manlike pasiënte moeiliker is om te behandel as hul vroulike eweknieë, aangesien mans soortgelyke uitkomste gehad het ten spyte van betekenisvol hoër dosisse radiojodium.

Low Temperature Nuclear Orientation (LTNO) is an important technique in the study of nuclei far from stability. The theory of LTNO and its application to the measurement of static nuclear moments and other quantities of spectroscopic interest are reviewed. The off-line facility at Oxford was used to study the decay of ¹³³I→¹³³Xe and ¹³⁵I→¹³⁵Xe. ¹³³I having Z=53 and N=80 has three protons above the closed shell Z=50 and two neutrons holes in N=82 shell, while ¹³⁵I has fully closed neutron shell since it has N=82, and they are of considerable theoretical interest since a wide variety of the theoretical nuclear models may be used to describe the observed levels close to the stable double closed shell structure. Another aim is to search for the nuclear magnetic dipole moment of the ground state of ¹³⁵I. Nuclear orientation of ¹³³IFe and ¹³⁵IFe enabled the mixing ratios of several transitions in the decay scheme of ¹³³I and ¹³⁵I to be determined. From temperature dependence for ¹³⁵I, the nuclear magnetic moment of ¹³⁵I has been deduced. Also temperature dependence for ¹³³I, analysed using a simple model, gave value for the magnetic hyperfine field that differed from previous published values. The method of combining nuclear orientation with NMR has become a very popular technique in recent years for determining nuclear magnetic dipole moments very precisely. The purpose of the NMR/ON experiment was to measure the hyperfine field with greater precision and to get some idea of the proportion of nuclei subject to it. Light Eu and Sm nuclei have attracted attention as systems with the number of protons right below the Z=64 subshell gap and the number of neutrons approaching N=82 major shell closure. Odd-proton, odd-neutron and odd-odd nuclei near the A=140 region have been investigated in the framework of the particle-triaxial rotor model. Main attention has been paid to explanation of experimental magnetic dipole and electric quadrupole moments of ground and isomeric states. Model predictions for deformation parameters of ^136-142Sm even-even cores have been extracted.