Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review.
Level 5 - mechanism / opinion, no new human data
Narrative methodological review evaluating the occupancy model and competition binding literature.
PubMed 10724107 · doi:10.1097/00004647-200003000-00001
What was done
The author reviewed literature across rodents, nonhuman primates, and humans evaluating the use of PET and SPECT radioligand competition techniques to measure acute fluctuations in synaptic dopamine concentration. The review critically assessed the standard occupancy model—which assumes radiotracer binding potential changes directly reflect receptor occupancy by endogenous dopamine—by comparing imaging signals against microdialysis measurements across various D2 and D1 radioligands (including benzamides, catecholamines, spiperone, and pimozide).
What was found
The abstract reports no quantitative values. Experimentally, altering dopamine synaptic levels consistently produced binding potential changes in benzamide and catecholamine D2 radiotracers that mirrored microdialysis-measured dopamine fluctuations. However, several findings contradicted the simple occupancy model: amphetamine-induced binding potential reductions for [123I]IBZM and [11C]raclopride lasted longer than extracellular dopamine elevations, and nonbenzamide D2 antagonists (spiperone, pimozide) and D1 tracers either showed no response or shifted in the opposite direction from model predictions. Agonist-induced receptor internalization was identified as a key factor influencing these interactions.
Why it matters
Validating dynamic neuroreceptor imaging allows noninvasive tracking of acute dopamine neurotransmission in neuropsychiatric disorders, but extending competition paradigms to other receptor systems requires accounting for complex cellular processes such as receptor internalization.
Limits
The review is narrative and the abstract does not report sample sizes, search criteria, or quantitative summary metrics. The underlying imaging model fails to explain prolonged binding reductions and divergent behavior across nonbenzamide and D1 radioligands.
Cited by
- supports Absolute dopamine concentrations can be measured directly in rodent brains, whereas in living humans researchers are limited to relative measurements of dopamine transmission.