Assessment of safety, efficacy, and dosimetry of a novel 18-kDa translocator protein ligand, [C]CB184, in healthy human volunteers.

BACKGROUND

N,N-di-n-propyl-2-[2-(4-[C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ([C]CB184) is a novel selective radioligand for the 18-kD translocator protein (TSPO), which is upregulated in activated microglia in the brain, and may be useful in positron emission tomography (PET). We examined the safety, radiation dosimetry, and initial brain imaging with [C]CB184 in healthy human volunteers.

RESULTS

Dynamic [C]CB184 PET scans (90 min) were performed in five healthy male subjects. During the scan, arterial blood was sampled at various time intervals, and the fraction of the parent compound in plasma was determined with high-performance liquid chromatography. No serious adverse events occurred in any of the subjects throughout the study period. [C]CB184 was metabolized in the periphery: 36.7% ± 5.7% of the radioactivity in plasma was detected as the unchanged form after 60 min. The total distribution volume (V ) was estimated with a two-tissue compartment model. The V of [C]CB184 was highest in the thalamus (5.1 ± 0.4), followed by the cerebellar cortex (4.4 ± 0.2), and others. Although regional differences were small, the observed [C]CB184 binding pattern was consistent with the TSPO distribution in the normal human brain. Radiation dosimetry was determined in three healthy male subjects using a serial whole-body PET scan acquired over 2 h after [C]CB184 injection. [C]CB184 PET demonstrated high uptake in the gallbladder at a later time (>60 min). In urine obtained approximately 100 min post-injection, 0.3% of the total injected radioactivity was recovered, indicating hepatobiliary excretion of radioactivity. The absorbed dose (μGy/MBq) was highest in the kidneys (21.0 ± 0.5) followed by the lungs (16.8 ± 2.7), spleen (16.6 ± 6.6), and pancreas (16.5 ± 2.2). The estimated effective dose for [C]CB184 was 5.9 ± 0.6 μSv/MBq.

CONCLUSIONS

This initial evaluation indicated that [C]CB184 is feasible for imaging of TSPO in the brain.