Comparative evaluation of Tc-MBIP-X/[C] MBMP for visualization of 18 kDa translocator protein

• Published in: New journal of chemistry 2019-07, Vol.43 (28), p.11288-11295
• Main Authors: Srivastava, Pooja, Kumari, Neelam, Kakkar, Dipti, Kaul, Ankur, Kumar, Pravir, Tiwari, Anjani K
• Format: Article
• Language: English
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/c9nj00180h

An elevated translocator protein (18 kDa, TSPO) density is observed during inflammation in the brain and peripheral organs making it a viable target for imaging. Recently, our group has explored a pharmacophore skeleton acetamidobenzoxazolone for positron emission tomography (PET) and single photon emission computed tomography (SPECT) applications to target TSPO. 2-(2-(5-Bromo/chloro benzoxazolone)acetamide)-3-(1 H -indol-3-yl)propionate (MBIP-Br/Cl) were synthesized by using tryptophan methyl ester and compared with 2-[5-(4-methoxyphenyl)-2-oxo-1,3-benzoxazol-3(2 H )-yl]- N -methyl- N -phenyl acetamide (MBMP) through tracer techniques. Computational docking showed similar results for MBIP-Br/Cl in comparison to MBMP. Their ex vivo and in vivo biodistributions were assessed in TSPO-rich organs as well as their release kinetics 0-120 min post injection. The ex vivo biodistribution showed a 7 fold higher uptake (5.16%ID per g vs. 0.72%ID per g) in the heart and a 2.5 fold higher uptake (12.91%ID per g vs. 4.69%ID per g) in the lungs for 99m Tc-MBIP-Cl compared to that of 99m Tc-MBIP-Br at 15 min. These findings demonstrated that 99m Tc-MBIP-Cl has improved pharmacokinetic properties compared to 99m Tc-MBIP-Br for SPECT application and is comparable to [ 11 C]MBMP. An elevated translocator protein (18 kDa, TSPO) density is observed during inflammation in the brain and peripheral organs making it a viable target for imaging.