ABSTRACT:Species differences occur in the brain concentrations of drugs, but the reasons for these differences are not yet apparent. This study was designed to compare brain uptake of three radiolabeled P-glycoprotein (P-gp) substrates across species using positron emission tomography. Brain concentrations and brain-to-plasma ratios were compared; and minipigs than in rats and guinea pigs. For example, the brainto-plasma ratio of [ 11 C]GR205171 was almost 9-fold higher in humans compared with rats. The species differences were still present after P-gp inhibition, although the increase in brain concentrations after P-gp inhibition was somewhat greater in rats than in the other species. Differences in plasma protein binding and metabolism did not explain the species-related differences. The findings are important for interpretation of brain drug delivery when extrapolating preclinical data to humans. Compounds found to be P-gp substrates in rodents are likely to also be substrates in higher species, but sufficient blood-brain barrier permeability may be retained in humans to allow the compound to act at intracerebral targets.

[(11)C]Cimbi-36 is currently the most promising candidate for investigation of 5-HT(2A) receptor agonist binding in the living human brain with PET.

Materials with persistent luminescence are attractive for in vivo optical imaging since they have a long lifetime that allows the separation of excitation of fluorophores and image acquisition for time-delay imaging, thus eliminating tissue autofluorescence associated with fluorescence imaging. Persistently luminescent nanoparticles have previously been fabricated from toxic rare-earth metals. This work reports that nanoparticles made of the conjugated polymer MEH-PPV can generate luminescence persisting for an hour long upon single excitation. A near-infrared dye was encapsulated in the conjugated polymer nanoparticle to successfully generate persistent near-infrared luminescence through resonance energy transfer. This new persistent luminescence nanoparticles have been demonstrated for optical imaging applications in living mice.

An 18F-labeled caspase-3 sensitive nano-aggregation PET tracer ([18F]CSNAT) was prepared and evaluated for imaging caspase-3 activity in doxorubicin-treated tumor xenografts. This enzyme-activatable PET tracer is designed to function in a novel mechanism – enhanced retention of the 18F activity in apoptotic tumors is achieved through intramolecular macrocyclization and in situ aggregation upon caspase-3 activation.