TABLE 2.

Criteria for passive diffusion of a radiotracer across the blood-brain-barrier (BBB) and good bioavailability (Lipinski et al., 2001; Clark, 2003; Waterhouse, 2003; Wong and Pomper, 2003; Pike, 2009; Van de Bittner et al., 2014).

Action	Characteristic	Requirement
Crossing BBB	Molecular weight	<450 g/mol
Crossing BBB	Polar surface area	<60–90 Å
Crossing BBB	Number of hydrogen bond donors	<5
Crossing BBB	Sum of nitrogen and oxygen atoms	<10
Crossing BBB	Log P (partition coefficient)	<4 (ideal range of 1–3.5)
Crossing BBB	Affinity for efflux pumps (e.g., P-gp)	Minimal
Crossing BBB	Affinity for enzymes at the BBB	Minimal
Crossing BBB	Brain uptake (%ID)	≥0.5%
	Brain uptake (SUV)	>2.0
Metabolism	Ionization at physiological pH	Low
Metabolism	Presence of radiometabolites in brain	Low
Binding to silent sites	Binding to plasma proteins	Low
Binding to silent sites	Non-specific or non-saturable sites	Low
Binding to target site	Kinetics quantifiable in vivo	Reversible or not completely irreversible
Binding to target site	Dissociation or inhibition constants	Nanomolar range
Binding to target site	Selectivity	High
Binding to target site	Specificity	High
Radiological safety	Whole-body and critical organ dosimetry	Low radiation dose

P-gp, P-glycoprotein; %ID, % injected dose; SUV, standard uptake value.