Radiotracers for SPECT brain imaging are divided into two classes: diffusible and not-diffusible radiotracers; this distinction lies in the ability (or not) to cross the blood-brain barrier (BBB).
The not-diffusible radiotracers - composed of ions or polar molecules - are unable to cross the lipid double layer of cell membranes, their brain accumulation, therefore, is an indication of an altered BBB permeability.
Classic examples of this group:
pertechnetate anion (99mTcO4-)
99mTc-DTPA
99mTc-sestaMIBI
201Tl-chloride
67Ga-citrate.
The diffusible radiotracers, capable of crossing the blood-brain barrier by passive transport, are neutral, lipophilic and low molecular weight molecules. Depending on their localization mechanism, they can in turn be divided into two subclasses: perfusion and receptor-binding radiotracers.
Perfusion radiotracers are located in the brain tissue proportionally to the blood flow (e.g. 99mTc-HMPAO and 99mTc-ECD). Once the blood-brain barrier has been overcome, a real "metabolic entrapment" takes place: the interaction of the radiopharmaceutical in fact, with cellular enzymes (i.e. phosphorylases) produces intermediate metabolites, unable to cross the cell membrane in one direction reverse. Different the clinical indications of brain perfusion studies: dementias (e.g. Alzheimer disease, Lewy bodies dementia), epilepsy (ictal-interictal perfusion SPECT), brain death diagnosis, brain perfusion reserve (acetazolamide test), etc.
Receptor-binding radiotracers (e.g. 123I-IBZM and 123I-ioflupane), instead, selectively interact with specific brain receptors (e.g. dopamine D2 and DaT, presynaptic dopamine transporters). Their distribution is therefore greater in those areas of the brain that selectively express target receptors (e.g. nigrostriatal region). Clinical indications: differential diagnosis of Parkinsonian syndromes.