Modified benzoxazolone (ABO-AA) based single photon emission computed tomography (SPECT) probes for 18 kDa translocator protein.

Acetamidobenzoxazolone (ABO) has been modified to ABO-AA, 2-(2-(5-bromo/chloro benzoxazolone)acetamide)-3-(1H-indol-3-yl)propionate to improve pharmacokinetics and lipophilicity (log p = 2.04). The final compound was synthesized in better yield and in fewer steps than previously reported MBIP-Br (70% vs. 62%). Computational docking confirmed binding of MBIP-Cl with translocator protein (TSPO) as well as with mutant TSPO (-8.99 for PDB: 4RYQ and -9.30 for PDB: 4UC1, respectively). Ex-vivo biodistribution and scintigraphy showed that 99m Tc-MBIP-Cl is better than 99m Tc-MBIP-Br in terms of uptake in TSPO-rich organs and release kinetics 0-120 min postinjection. At 15 min, uptake was 2.75-fold (12.91%ID/g vs. 4.69%ID/g) in lung and seven-fold (5.16%ID/g vs. 0.72%ID/g) in heart for 99m Tc-MBIP-Cl compared to that of 99m Tc-MBIP-Br which gives warrant to utilize this single photon emission computed tomography agent in higher animals.