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 99mTc‐MBIP‐Cl is better than 99mTc‐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 99mTc‐MBIP‐Cl compared to that of 99mTc‐MBIP‐Br which gives warrant to utilize this single photon emission computed tomography agent in higher animals.