Brain Receptor Scintigraphy

Brain receptor scintigraphy is a nuclear medicine procedure used to visualize the transmission of information between nerve cells by radioactively labeled neurotransmitters (biochemical messengers between nerve cells). The cells of the central nervous system (CNS) are equipped with axons (long cell extensions) through which information/stimuli can be transmitted as electrical potentials. However, the connection points between the nerve cells cannot simply be passed by electrical charges, so that the electrical stimulus must be converted into a biochemical one. This occurs at the synapse (cell-cell contact with excitation transmission function), where the incoming excitation of a cell leads to neurotransmitter release into the synaptic cleft. The neurotransmitter diffuses through the synaptic cleft and binds to specific receptors on the postsynaptic (downstream) neuron, exciting it. The stimulus can be electrically transmitted again in this cell or, if necessary, trigger other cellular responses. There are various central nervous diseases that are associated with disturbances in the correct transmission of information at synapses (e.g. Parkinson’s disease). Different phases of action of the neurotransmitter such as its formation, specific receptor interaction or reuptake may be impaired, resulting in overexcitation or underexcitation of the downstream nerve cell. The principle of nuclear medicine examination is based on visualizing synaptic neurotransmission with radioactively labeled receptor ligands (binding partners of the receptors). Depending on the indication, the appropriate ligand for the transmitter system is used, applied (administered) intravenously, and then its accumulation is measured using the emitted radioactivity.

Indications (areas of application)

Imaging of brain receptors allows a statement to be made about the correct function of neurotransmission. Functional disorders can thus be detected at a very early stage, in some cases before the appearance of morphologic changes or even clinical symptoms. Brain receptor scintigraphy can be used for (suspected of):

  1. Basal ganglia diseases: Parkinson’s disease, Parkinson syndromes, Wilson’s disease, Huntington’s disease, tremor syndromes.
    • Diseases of the basal ganglia cause movement disorders. Depending on the localization and type of damage, different clinical symptoms dominate: rigor (increased muscle tone), tremor (trembling), akinesia (high-grade lack of movement) or overshooting movements (typical of Huntington’s disease).
    • The triad of rigor, tremor and akinesia is a typical symptom complex known as Parkinsonism. The cause is usually Parkinson’s disease, but other neurodegenerative diseases may also play a role. Depending on the cause, different basal ganglia parts are affected.
    • Brain receptor scintigraphy offers the possibility, for example, by imaging the dopaminergic system (synapses in which dopamine is used as a neurotransmitter), to determine the localization of the basal ganglia disorder and thus allows a differential diagnosis of movement disorders.
  2. Epilepsy (seizure disorder): radiolabeled benzodiazepine receptor antagonists are used, which have decreased receptor binding in the seizure-inducing focus so that it can be detected in its localization. This is explained in part by local nerve cell loss.

Contraindications

Relative contraindications

  • Lactation phase (breastfeeding phase) – breastfeeding must be interrupted for 48 hours to prevent risk to the child.
  • Repeat examination – no repeat scintigraphy should be performed within three months due to radiation exposure.

Absolute contraindications

  • Gravidity (pregnancy)

Before the examination

Depending on the neurotransmitter system under investigation, care must be taken to discontinue any medications taken in a timely manner. For example, dopamine receptor antagonists used in Parkinson’s disease must be discontinued, if possible, one week before brain receptor scintigraphy is performed to allow unbiased assessment of dopamine receptors.

The procedure

  • The radiopharmaceutical (tracer) is applied intravenously to the patient.Mostly radioactively labeled receptor antagonists (bind to and inhibit the receptor) are used, which have a higher affinity for the receptors and are degraded more slowly than natural ligands (receptor binding partners). Furthermore, the radiopharmaceutical requires sufficient lipophilicity (fat solubility) to cross the blood-brain barrier.
  • After application, a sufficient distribution time of the tracer should be observed. After passage of the blood-brain barrier, most receptor ligands initially undergo perfusion-dependent (blood flow-dependent) accumulation, which is, however, irrelevant for the study. Between application and measurement, the time interval is therefore often several hours.
  • In principle, radiolabeled ligands are available for almost all transmitter systems and some are used for research purposes. Most clinically relevant are dopamine receptor antagonists ([18F]FDOPA,FP-CIT) and benzodiazepine receptor antagonists ([123I]iomazenil).
  • The measurable enhancement intensity depends on the regional density and affinity of the neuroreceptors present, which in turn correlates with the type and severity of the disease.
  • Radioactivity is detected using single photon emission computed tomography (SPECT) systems with the advantage of cross-sectional imaging.

Possible complications

  • Intravenous application of radiopharmaceutical may result in local vascular and nerve lesions (injuries).
  • Radiation exposure from the radionuclide used is rather low. Nevertheless, the theoretical risk of radiation-induced late malignancy is increased, so that a risk-benefit assessment should be performed.