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DC Field | Value | Language |
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dc.contributor.advisor | Valliant, John Fitzmaurice | en_US |
dc.contributor.author | Gullon, Janet Teri | en_US |
dc.date.accessioned | 2014-06-18T16:46:47Z | - |
dc.date.available | 2014-06-18T16:46:47Z | - |
dc.date.created | 2011-06-03 | en_US |
dc.date.issued | 2010-04 | en_US |
dc.identifier.other | opendissertations/4493 | en_US |
dc.identifier.other | 5511 | en_US |
dc.identifier.other | 2045199 | en_US |
dc.identifier.uri | http://hdl.handle.net/11375/9362 | - |
dc.description.abstract | <p>This thesis demonstrates the versatility of the carborane cage by qsing a known carborane containing analogue of the amino acid phenylalanine, carborananylalanine (Car<br /><strong>5</strong>) as a novel platform for radio labelling targeting vectors with both <sup>99m</sup>Tc and <sup>125</sup>I. Initial racemic synthesis of Car was undertaken based on a literature procedure. Optimization of the procedure yielded all key intermediates leading to <em>closo</em>-carboranylalanine which was obtained in 67% yield. A new method for cage degradation of Car <strong>5</strong> involving microwave heating in water to give the desired <em>nido</em>-Car <strong>9</strong> was developed such that the product could be isolated in quantitative yield where the only additional product was boric acid. The removal of boric acid was non-trivial but was ultimately achieved through conversion to the more volatile borate ester.</p> <p>The synthesis of Re-Car <strong>12</strong> was achieved by microwave heating <em>nido</em>-Car <strong>9</strong> with [Re(CO)<sub>3</sub>(H<sub>2</sub>O)<sub>3</sub>]Br at 180<sup>∘</sup>C for 15 min in a microwave. The reaction produced multiple carborane products including the desired product <strong>12</strong>, an amino acid rhenium chelate complex <strong>15</strong>, and a di-rhenium complex <strong>14</strong>. Conditions were altered to maximize the amount of the desired compound which was separated from impurities through semipreparative HPLC albeit in low yield (3%). Analysis of <strong>12</strong> by <sup>1</sup>H nOe NMR experiments revealed that cage isomerization had occurred under the employed conditions resulting in the formation of the 2, 1, 8-cage isomer of <strong>12</strong>.</p> <p>The iodination of nido-Car was found to take place in high yield at room temperature with a reaction time of less than 10 minutes. When the stoichiometry was kept to a 1:1 ratio between <strong>9</strong> and I<sub>2</sub> no other side products were observed and purification by semi-preparative HPLC gave pure I-Car <strong>16</strong> in 48% yield.</p> <p>It was found that the radiolabelling of nido-Car with <sup>99m</sup>Tc proceeded with very few side products as compared to the cold rhenium standard (Re-Car <strong>12</strong>). Variations of the labelling conditions (time, temperature and pH) resulted in a 45% percent conversion to the desired <sup>99m</sup>Tc_Car <strong>13</strong>. The HPLC retention time of the <sup>99m</sup>Tc product correlated to the Re-Car <strong>12</strong> reference standard.</p> <p>Radiolabelling of <em>nido</em>-Car with <sup>125</sup>I using Iodogen<sup>®</sup> as an oxidant was fast, efficient and high yielding. It was found that under the standard labelling conditions, <em>nido</em>-Car would give high conversion (>95%) to <sup>125</sup>I_Car <strong>18</strong> in less than 10 minutes at room temperature. Not only was <strong>9</strong> highly reactive towards radioiodination, but the resulting product was found to be remarkably stable with no signs of degradation up to two weeks.</p> <p>A dilution study to examme the reactivity of <strong>9</strong> towards radioiodination was performed. At concentrations of 4.5 mM and 2.3 mM the conversion of <strong>9</strong> to <sup>125</sup>I-Car <strong>18</strong> occurred in >95% conversion and 70% conversion occurred at a ligand concentration of 1.1 mM. A head-to-head experiment using equimolar amounts of tyrosine to <em>nido</em>-Car was also performed and found that <sup>125</sup>I-Car was formed prefentially with an average percent conversion of 93%.</p> <p>This work demonstrates that a versatile radiolabelling platform using carboranes can be developed. Because the ligand is a non-natural amino acid it can serve for preparing bioconjugates and targeted molecular imaging and therapy agents.</p> | en_US |
dc.title | The Preparation of Metallocarborane and Iodinated Carborane Amino Acid Analogues for Molecular Imaging and Therapy | en_US |
dc.type | thesis | en_US |
dc.contributor.department | Chemistry | en_US |
dc.description.degree | Master of Science (MS) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
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fulltext.pdf | 3.64 MB | Adobe PDF | View/Open |
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