Comparative evaluation of 99mTc-MBIP-X/11[C] MBMP for visualization of 18 kDa translocator protein

New Journal of Chemistry Pub Date: 2019-06-11 DOI: 10.1039/C9NJ00180H

Abstract

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-(1H-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(2H)-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 99mTc-MBIP-Cl compared to that of 99mTc-MBIP-Br at 15 min. These findings demonstrated that 99mTc-MBIP-Cl has improved pharmacokinetic properties compared to 99mTc-MBIP-Br for SPECT application and is comparable to [11C]MBMP.

Graphical abstract: Comparative evaluation of 99mTc-MBIP-X/11[C] MBMP for visualization of 18 kDa translocator protein
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