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| Home > Publications database > Development of no-carrier-added radioselenation methods for the preparation of radiopharmaceuticals |
| Dissertation / PhD Thesis/Book | PreJuSER-37411 |
2003
Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag
Jülich
Please use a persistent id in citations: http://hdl.handle.net/2128/235
Report No.: Juel-4044
Abstract: The radioisotope selenium-73 (half-life: 7.1 h, positron-branching: 65 %) is an interesting label for application in positron emission tomography, serving as a possible substitute of sulfur in thio compounds of interest. Furtheron, the half-life of selenium-73 offers the possibility to study relatively slow pharmacokinetics of selenated radiotracers. Previous methods for labelling with radioselenium suffered from the drawback of an indispensable addition of (nat)Se-carrier, resulting in tracers of low specific activity. In consideration of the possible toxicity of selenium compounds, two new radiosynthetic pathways were developed in this work for the preparation of Se-73-labelled compounds at the no-carrier-added (n.c.a.) level. Selenium-75 (half-life: 120.4 d) was used for the development and optimization of these radiosyntheses. The first method developed started with a homogenous or polymer-supported reaction of elemental n.c.a. Se-75 with an isocyanide and subsequently an amine. Radioselenoureas formed were alkylated via alkyl triflates to yield the corresponding Se-75-labelled selenouronium salts, which were purified afterwards. Hydrolysis under basic conditions and a subsequent second alkylation yielded various asymmetric n.c.a. Se-75-labelled dialkyl selenoethers with a radiochemical yield of 13 to 56 % (related to elemental Se-75) depending an the substituents. The use of the polymer-supported pathway provides the advantages of a shorter reaction time (35 min in comparison to 130 min in homogenous phase) and a more convenient separation of Se-75-labelled intermediates, thus appearing very attractive for automation. Subsequently, Se-73-labelled model compounds such as benzylmethylselenide and 1-phenyl-1-(propylseleno) ethane were synthesized using the optimized reaction conditions. The second labelling method was based an the initial reaction of elemental n.c.a. Se-75 with sodium cyanide, yielding sodium radioselenocyanate. Treatment of this intermediate in situ with alkyl bromides resulted in Se-75-labelled alkyl selenocyanates. After separation via reversed phase cartridges, the alkyl radioselenocyanates reacted with organic lithium or Grignard compounds to asymmetric Se-75-labelled selenoethers with a radiochemical yield of 9 to 55 % (related to elemental Se-75) depending an the substituents. This pathway offers the advantage to generate both aliphatic and aromatic radioseleno compounds by using appropriate alkyl or aryl lithium or Grignard compounds. The new approaches to n.c.a. labelling with radioselenium developed in this work extensively enlarge the availability of Se-73,75-labelled compounds. In particular, a method is described for the first time to prepare n.c.a. aryl radioselenoethers. For proof of identity via radioanalysis appropriate radio high performance liquid chromatography and radio thin layer chromatography methods were developed. Several non-radioactive seleno compounds, which served as reference substances, were prepared for the first time. Besides various simple asymmetric selenoethers, two more complex, physiologically relevant molecules, i.e. the c.a. Se-75-labelled amino acid derivative L-homocysteine selenolactone and the n.c.a. Se-75-labelled adenosine A(1) receptor ligand 5'-(methylseleno)-N(6)-cyclopentyladenosine, were synthesized using preferentially the selenourea method with total radiochemical yields of 20 - 30 (related to elemental Se-75).
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