One of the most sensitive imaging devices for observing dopamine receptors is positron emission tomography (PET), a non-invasive technique. PET uses a radioactive tracer that binds to the receptors, allowing researchers to track receptor distribution in real time. Dopamine receptor imaging is performed with radiolabelled ligands that are labelled for D1, D2, and other dopamine receptor subtypes. And because PET can track the binding of these ligands, we know receptor abundance, presence and activity real-time. Whether a drug candidate actually hits the dopamine receptors, the speed with which the drug spreads in the brain, and the moment when the receptors are flooded with a new one is all we can say from PET when designing drugs. Not only that, but PET can also pick up on receptor modulation during neurological pathology – a hugely useful clue when aiming drugs at influencing dopamine signalling.

Figure 1. Imaging of dopamine receptors (D1 and D 2/3) in the corpus striatum of the pig brain (red area). (Heindl C, et al.; 2008)

Single-Photon Emission Computed Tomography (SPECT)

Single-Photon Emission Computed Tomography (SPECT) offers 3D maps of receptor distribution with radiolabelled tracer like PET. PET is finer resolution, while SPECT is much cheaper and used in most clinical research on dopamine receptors. SPECT is especially useful to measure brain volume that's bound by dopamine receptors and see if drugs interfere with binding. SPECT-imaging followed changes in dopamine receptors in Parkinson's and Huntington's disease. Through following the way radiolabelled ligands associate with dopamine receptors, researchers can better understand how these diseases arise, and experiment with drugs. MRI and fMRI: Magnetic resonance imaging (MRI)/Functional MRI. The usual imaging choice is MRI to do structural measurements, but there is an alternative option – functional MRI (fMRI) – that can measure brain activity via neurotransmitters like dopamine. fMRI scans for variations in the blood-flow patterns, which are caused by neuronal firing during dopamine receptor stimulation. This is particularly helpful when it comes to the brain's reward system and how it responds to drug treatments. We can use fMRI in drug discovery to track how a drug behaves in the brain, such as on dopamine receptors. If we can track changes in dopamine-signalling regions of the brain, researchers can keep track of whether dopamine-sensitisers work and adapt their dosage. Optogenetics and Imaging New technology is optogenetics – the controlled illumination of the dopamine receptors. When neurons are gene edited to encode light-sensitive ion channels, researchers can turn on and off animal dopamine receptor subtypes. Together with imaging – two-photon microscopy, for instance – optogenetics also gives us unprecedented access to receptors, and high-resolution photographs of the behaviour of receptors, on demand. This approach is particularly helpful in the murky realm of dopamine receptor signalling and behaviour. With the use of optogenetics in the design of drugs, the functional value of altering dopamine receptor activity could be assessed and subtypes of receptors identified as potential target drugs.

Our Services

Dopamine Receptors Imaging Analysis

Used for Preclinical and Clinical Drug Development

If drugs are assessed on dopamine receptors in an image, we can optimise candidate drugs, even predict their clinical effects. Preclinical Drug Development Preclinical imaging – PET, SPECT, optogenetics – allows researchers to assess how drugs might act in animals. For instance, PET-scanning of radiolabelled ligands can tell us how well a drug has the pharmacokinetics of a drug – how far into the brain, how easily it targets receptors, and so on. It is important to use that data when formulating dose regimens and choosing the best candidate drugs for clinical trials. Imaging can also identify off-target or unexpected interactions with dopamine receptors, and ultimately lead to better candidate drugs. While imaging also can be used to diagnose dopamine receptors as the cause of neurological conditions, we can design drugs that are more effective and less toxic with receptor subtypes. Clinical Drug Development Dopamine receptor imaging for drug effects is available in human trials. It's possible for PET/SPECT to show receptor presence and distribution, as well as clinical correlation. Whether a drug hits the right dopamine receptors and inhibits them in the right brain can be determined from imaging studies in Parkinson's or schizophrenia trials, for instance. Dopamine receptor imaging can also help to detect biomarkers of progression of disease or drug efficacy — and so offer more targeted, targeted therapies. In psychiatric disorders, where receptor signalling is often dysfunctional, scans can show pathology, and the clinician how well a drug is working. Challenges and Future Directions There is much that dopamine receptor imaging has done to get drugs discovered, but still the barriers remain. The only blemish is imaging resolution – especially when the number of receptors, or small differences in receptor function, are small. What's more, radiolabeled tracers are logistically and regulatoryly tricky, so there are some imaging techniques not easily accessible. Yet imaging of the future – with specificer ligands, more detailed scanners, new non-invasive techniques – will unravel these limits. Imaging along with other biomarkers and genetic data will also be the engine of personalized medicine going forward — it will help create better, more precise drugs. Conclusion So many neurological and psychiatric disorders are built on dopamine receptors that they are prime targets for therapy. Imaging science has reconstructed the distribution, activity and activity of dopamine receptors so that drugs can be programmed to act on them with great accuracy and specificity. From preclinical to clinical studies, PET, SPECT and optogenetics scans are essential parts of treatments that try to restore dopamine to the brain. As imaging improves, the future of drug discovery and precision medicine is indeed theirs.

1. Heindl C, et al.; Refinement and reduction in animal experimentation: options for new imaging techniques. ALTEX. 2008, 25(2):121-5.

*If your organization requires the signing of a confidentiality agreement, please contact us by email.

Please note: Our services can only be used for research purposes. Do not use in diagnostic or therapeutic procedures!