Discovery | Identification of candidate structures; in vitro testing for best compounds; optimization of radiolabeling | Good yield, high specific activity, stability |
Assessment | Affinity | Postmortem human brain homogenates or sections, Ki < 1 nM |
| Selectivity | >200-fold selectivity |
| Lipophilicity | Log D7.4 = 2 to 3.5 |
| Stability | 4 half-lives |
| Blood–brain barrier | P-glycoprotein substrate (MDR1-MDCK) < 20 |
| Metabolite identification | Ex vivo analysis (characterize all major metabolites with radiolabel) |
Validation | Correlation and safety | High signal-to-noise ratio; correlation with histopathology; correlation with clinical dosimetry |
| Quantitative accuracy | Full kinetic modeling, including arterial input function corrected for metabolites; streamlining of protocol for clinical use; testing–retesting of all outcome measures |
Application | Logistic feasibility | Production/distribution network; imaging site technical standardization |