This thesis describes the application of the radioisotope 11C to the synthesis of two
analogues of the neurohormone melatonin. The labelled compounds were intended to be
used as tracers for the medical imaging technology Positron Emission Tomography (PET).
[
11C]Carbon dioxide, produced in a small on-site cyclotron by the nuclear reaction
14N(p,a)11C, was converted into [11C]CH3COC1 by reaction first with CH3MgBr, followed
by reaction with phthaloyl dichloride. The labelled acid chloride was distilled into a
solution of an amine, yielding the corresponding 11C-labelled amide, which was purified
by a simple solid-phase extraction method.
An apparatus was designed and built that allowed the remote synthesis with
several hundred millicuries of [11C]C02• The apparatus was mounted in a hot cell and
operated remotely with a Macintosh Powerbook programmed in Hypercard. The apparatus
and software are generic for these acylation reactions.
The individual reaction steps were optimized in terms of reaction time, solvents
and equipment; radiosyntheses of a number of purified labelled acetamides were
completed in 35 minutes. The radiochemical yields ranged from 15 to 20% with specific
activities in the 500 mCi/J..tmol range at the end of the synthesis.
2-Iodo-[11C-acetyl]melatonin (11) and 7-methoxynaphthylenyl-1-ethyl-N-[11Cacetyl]
acetamide (15) were synthesized for the first time for PET studies. It was shown
that both compounds readily cross the blood-brain-barrier and penetrate into all brain
tissues. Specific binding to the melatonin receptors in the suprachiasmatic nuclei of the
hypothalamus could not be visualized with either one of the 11C-labelled ligands because
of low specific activity and high nonspecific binding. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22643 |
| Date | 04 1900 |
| Creators | Schulze, Brita G. |
| Contributors | McCarry, Brian E., Chemistry |
| Source Sets | McMaster University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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