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Ligand-receptor interaction modelling using PET imaging

Zamuner, S. (2003). Ligand-receptor interaction modelling using PET imaging. (Unpublished Doctoral thesis, City, University of London)


A basic problem in the discovery and development of novel drugs to be used in the treatment of neurological and psychiatric disorders is the absence of relevant in vitro or in vivo animal models that can yield results which can be extrapolated to man. Drug research now benefits from the fast development of functional imaging techniques such as positron emission tomography (PET) which trace radiolabelled molecules directly in the human brain. PET uses molecules that are labelled with short-lived radionuclides and injected intravenously into experimental animals, human volunteers or patients.

The current work provided novel knowledge in the ligand-receptor interaction between GR205171 and neurokinin 1 (NK1) receptor. GR205171 is a high affinity and selective NK1-receptor antagonist. Clinical studies were performed both in monkeys and humans to obtain information about the suitability of the ligand with regard to its affinity and penetration.

The specific objectives of this thesis were to define an appropriate model for GR205171 tracer and to calculate receptor occupancy in the monkey and human brain, introducing also novel methodological approaches. The definition of a relationship between plasma drug concentration and receptor occupancy was another important aim of this work. In fact, the demonstration of quantitative relationships between drug binding in vivo from plasma concentration data and drug effects in patients can be used to validate targets for drug action, to correlate pharmacological and physiological effects, and to optimise clinical treatment.

In conclusion, the modelling of GR205171 PET data, including different methodological approaches, demonstrated its utility in assessing NK1 receptor occupancy after drug challenge and its relationship with plasma concentration.

Publication Type: Thesis (Doctoral)
Subjects: Q Science > QA Mathematics > QA75 Electronic computers. Computer science
R Medicine
Departments: School of Science & Technology > Computer Science
School of Science & Technology > School of Science & Technology Doctoral Theses
Doctoral Theses
[thumbnail of Zamuner thesis 2003 PDF-A.pdf]
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