University of Groningen
Development of 18F-labeled agonist radioligands for PET imaging of the high-affinity state of
cerebral dopamine D2/3 receptors
Shalgunov, Vladimir
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2017
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Shalgunov, V. (2017). Development of 18F-labeled agonist radioligands for PET imaging of the high-affinity
state of cerebral dopamine D2/3 receptors. University of Groningen.
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Propositions
Belonging to the thesis
“Development of 18F-labeled agonist radioligands for PET imaging of
the high-affinity state of cerebral dopamine D2/3 receptors”
by Vladimir Shalgunov
1. In pharmacokinetic and biodistribution studies, the advantage of the radioactive label is that it does not have to be extracted from the tissue for quantification, and the intensity and type of radioactive decay are independent of the environment (Chapter 1).
2. For G-protein coupled receptor ligands, agonism does not automatically imply preference for the “high-affinity state” of the receptors (Chapter 2).
3. Although some instances of failed attempts to detect the high-affinity state of G-protein coupled receptors in vivo may have resulted from insufficient characterization of the selectivity and intrinsic activity of the radioligands used for detection, in general these failures point to a gap in our understanding of the functioning of G-protein coupled receptors (Chapter 2).
4. The advantage of the 7-hydroxy-2-aminomethylchromane scaffold as a starting point in dopamine D2 receptor radioligand development is that it offers
convenient possibilities to accommodate the 123I or 18F label on the N-substituent, and the same substituent can also be used to adjust the lipophilicity of the candidate radioligands (Chapter 3).
5. The “stickiness” of dried [18
F]fluoride is particularly detrimental for microchannel setups, because of the high surface-to-volume ratio of the environment and the fact that drying and labelling processes take place in different locations (Chapter 6).
6. Despite great acceleration in reaction speeds, microchannel radiosynthesis systems do not provide a lot of time saving unless [18F]fluoride preparation is also miniaturized (Chapter 6).
7. New comprehensive studies that would assess the relative abundance of the high-affinity state in the same G-protein coupled receptor population using membrane homogenates, dispersed intact cells, and live animals, would shed more light on the reasons behind the current confusion regarding the existence of the high-affinity state of G-protein coupled receptors in vivo (Chapter 8).
8. Dopaminergic receptor imaging in clinical research is likely to benefit more from a novel tracer selective for dopamine D2 or D3 receptor subtypes, even if it be an
antagonist, than from a novel agonist tracer that binds indiscriminately to both named receptor subtypes (Chapter 8).
9. Research is when you do something and then find out you have done it all wrong. 10. Time spent on failures is not completely wasted if one comes to understand the
reasons behind failures.
11. Heavy buttocks are as important for a successful researcher as sharp brain. 12. Being able to integrate into and work in a team is a crucial skill if you want to be
