Receptor Occupancy Imaging Studies in Oncology Drug Development.
Ingrid J G Burvenich1,2, Sagun Parakh1,2,3, Adam C Parslow1,2
1Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Australia.
The AAPS Journal
|March 10, 2018
Summary
Molecular imaging, including PET and SPECT, helps determine optimal therapeutic doses by assessing drug delivery and target engagement. Early imaging studies improve drug development, dose selection, and patient stratification for better treatment outcomes.
Area of Science:
- Oncology
- Radiology
- Pharmacology
Background:
- Therapeutic dose selection for tumors is complex.
- Molecular imaging techniques like PET and SPECT can answer key questions about drug efficacy.
- Combining functional and anatomical imaging aids in understanding treatment effects.
Purpose of the Study:
- To review the value of translational receptor occupancy studies and molecular imaging in early drug development.
- To highlight how imaging can optimize therapeutic dose selection.
- To explore improvements in patient stratification for enhanced drug utility.
Main Methods:
- Utilizing positron emission tomography (PET) and single-photon emission computed tomography (SPECT) for molecular imaging.
- Integrating functional imaging (PET/SPECT) with anatomical imaging (MRI/CT).
- Conducting in vivo competition studies with specific radioligands to assess drug-target interactions.
Main Results:
- Molecular imaging assesses drug reach, target engagement, dose sufficiency, and target saturation.
- Combined imaging modalities allow correlation of drug occupancy with anatomical/physiological changes.
- In vivo studies directly link drug plasma concentration to target occupancy.
Conclusions:
- Early integration of molecular imaging and receptor occupancy studies is crucial for effective drug development.
- Imaging aids in precise therapeutic dose selection and refinement.
- Improved patient stratification through imaging can maximize drug effectiveness post-approval.
Keywords:
drug developmentpositron emission tomography (PET)receptor imagingreceptor occupancysingle–photon emission tomography (SPECT)More Related Videos
Related Concept Videos
01:25Drug-Receptor Bonds
4.8K
Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...
In...
4.8K
01:29Drug-Receptor Interactions
7.6K
Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
7.6K
01:28Drug-Receptor Interaction: Antagonist
5.1K
An antagonist is a drug that binds strongly to a receptor without activating it. An antagonist prevents other molecules, such as neurotransmitters or hormones, from binding to the receptor and triggering a cellular response. Such interaction effectively hinders the normal physiological processes mediated by the receptor, resulting in various pharmacological effects depending on the specific receptor targeted.
Antagonists can be classified as competitive or noncompetitive based on their...
Antagonists can be classified as competitive or noncompetitive based on their...
5.1K
01:25Drug-Receptor Interaction: Agonist
4.2K
Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
4.2K
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
2.8K
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
2.8K
01:20Antiasthma Drugs: Muscarinic Receptor Antagonists
1.8K
Muscarinic receptor antagonists, also known as antimuscarinic agents, are a class of bronchodilators used to treat asthma, although they are more commonly used to treat COPD. They work by inhibiting the action of acetylcholine (ACh), a neurotransmitter, on muscarinic receptors found in the airways.
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...
1.8K