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Synthesis and evaluation of gadolinium based MRI agents consisting of cationic complexes

Rana, Adeel Ahmad
Master thesis
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Year
2006
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http://urn.nb.no/URN:NBN:no-13994

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  • Farmasøytisk institutt [1364]
Abstract
Syntheses of three macrocyclic gadolinium based cationic complexes (Gd-DO3A-HNTPAC, Gd-DO3A-NTABI and Gd-DO3A-NTOBAC) were attempted. The idea of synthesizing gadolinium based cationic complexes, was based on the possibilities of mimicking 99mTc-sestamibi and 99mTc-tetrofosmin ability to be taken up by myocardial cells, or mimicking the ability of edrophonium and neostigmine to bind to the AChE in the heart s conduction system and sensory nerves. The goal was to determine the target molecules relaxivities and biodistribution, and to determine whether they would act as organ-specific (heart-specific) or as extracellular fluid agents.

The target molecules proved to be difficult to synthesize and purify. MS(ES+) and TLC indicated that one of the target molecules (Gd-DO3A-HNTPAC) was made. The purification process with flash chromatography and ion exchange chromatography of Gd-DO3A-HNTPAC proved to be very challenging. Finding of a purification method for Gd-DO3A-HNTPAC may have succeeded, but requires further optimization. NMR (1H NMR and 13C NMR), MS(ES+), TLC and HPLC were used as analyses methods throughout this work.

Thus, the relaxivities and biodistribution of the target molecules could not be determined. More time was required to finish preparation of the target molecules before any further tests on contrast effect and pharmacokinetics could be carried out.
 
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