Title:PET Tracers for Imaging of ABC Transporters at the Blood-Brain Barrier: Principles and Strategies
Volume: 22
Issue: 38
Author(s): Gert Luurtsema, Philip Elsinga, Rudi Dierckx, Ronald Boellaard and Aren van Waarde
Affiliation:
Keywords:
PET, BBB, efflux transporters, P-gp, BCRP, MRP1, radiotracers, quantification.
Abstract: ABC transporters at the human blood-brain barrier protect the brain against the
entry of harmful compounds but may also limit (or prevent) the cerebral entry of therapeutic
drugs (e.g. anti-epileptics, antidepressants and antipsychotics). The efflux function of these
transporters may be impaired in neurodegenerative disorders like Alzheimer and Parkinson
disease. For such reasons, there is much interest in modulation of the efflux function of ABC
transporters and in the monitoring of this function with positron emission tomography
(PET). The efflux function of P-glycoprotein, an important member of the ABC transporter
family, can be quantified with the PET tracer (R)-[11C]verapamil, but the lipophilicity of this
probe and the formation of radioactive metabolites which enter the brain complicate such
measurements considerably. (R)-[11C]verapamil is also not very suitable for the detection of
P-gp upregulation, as may occur in epilepsy or drug resistance. Current radiochemical efforts
are therefore focused on the development of PET probes with improved characteristics,
for example; capability to detect both up- and down regulation of transporter function and expression, a better
metabolic profile (no brain-entering metabolites), reduced lipophilicity and a longer physical half-life (labeling
with 18F instead of 11C).