<p>Different prosthetic groups containing a trialkylstannyl- and an electrophilic group have been synthesised and labelled with the accelerator produced <sup>76</sup>Br (T<sub>1/2</sub>=16 h) through oxidative bromination. The labelled prosthetic groups were conjugated to amino-containing macromolecules such as proteins and 5´-modified oligonucleotides.</p><p><i>N</i>-Succinimidyl 4-[<sup>76</sup>Br]bromobenzoate <b>14 </b>was synthesised in 65 % radio-chemical yield and was conjugated to 5´-hexylamino-modified phosphodiester and phosphorothioate oligonucleotides in 12-19 % isolated radiochemical yield. The stability of the <sup>76</sup>Br-oligonucleotide-conjugates <i>in vivo</i> in rats was investigated. No degradation from the 5´-end, resulting in labelled, low molecular weight compounds was detected. Compound <b>14</b> has also been used for labelling of different proteins in 23-61% radiochemical yield.</p><p><i>N</i>-Succinimidyl-5-[<sup>76</sup>Br]bromo-3-pyridinecarboxylate <b>17</b> and methyl-4-[<sup>76</sup>Br]bromo-benzimidate <b>15 </b>were synthesised from the corresponding trimethylstannyl-compound in 25% and 40 % yield respectively. Compounds <b>14 </b>and <b>17</b> were conjugated to ε-Boc-octreotide in 55 and 50% isolated radiochemical yield respectively after microwave heating. Compound <b>15</b> did not react with octreotide under the conditions investigated. The two <sup>76</sup>Br-labelled octreotide derivatives showed different lipophilicity and different binding-properties to tissue from meningiomas.</p><p>Hyaluronic acid, a polysaccharide, was modified with tyramine and labelled by oxidative bromination using <sup>76</sup>Br in 10% radiochemical yield.</p><p>The generator produced <sup>68</sup>Ga (T<sub>1/2</sub>=68 min) was used to label octreotide and oligonucleotides modified with the metal chelating group 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid (DOTA). <sup>68</sup>Ga-DOTA-octreotide was isolated in 65% radiochemical yield and a phosphorothioated <sup>68</sup>Ga-DOTA-oligonucleotide was isolated in 35% radio-chemical yield after 30 min synthesis time.</p><p>Compound<b> 14 </b>was reacted with 3-aminomethylbenzylamine to give compound <b>18</b>. The specific radioactivity<b> </b>of<b> 18 </b>was determined to be 36 GBq/µmol by measuring the ratio between the mass-peaks for the <sup>76</sup>Br and <sup>79</sup>Br-compounds using packed-capillary LC-MS.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-595 |
| Date | January 2001 |
| Creators | Yngve, Ulrika |
| Publisher | Uppsala University, Department of Chemistry, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1104-232X ; 605 |
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