Dosimetry and efficacy of a tau PET tracer [¹⁸F]MK-6240 in Japanese healthy elderly and patients with Alzheimer’s disease

A new tau PET tracer [¹⁸F]MK-6240 has been developed; however, its dosimetry and pharmacokinetics have been published only for a European population. This study investigated the safety, radiation dosimetry, pharmacokinetics and biodistribution of [¹⁸F]MK-6240 in Japanese elderly subjects. Also, the pattern and extent of brain retention of [¹⁸F]MK-6240 in Japanese healthy elderly subjects and patients with Alzheimer’s disease (AD) were investigated. These Japanese results were compared with previous reports on non-Japanese.

Three healthy elderly subjects and three AD patients were enrolled. Dynamic whole-body PET scans were acquired for up to 232 min after starting injection of [¹⁸F]MK-6240 (370.4 ± 27.0 MBq) for the former, while a dynamic brain scan was performed from 0 to 75 min post injection for the latter. For both groups, brain PET scans were conducted from 90 to 110 min post injection. Sequential venous blood sampling was performed to measure the radioactivity concentration in the whole blood and plasma as well as the percentages of parent [¹⁸F]MK-6240 and radioactive metabolites in plasma. Organ doses and effective doses were estimated using the OLINDA Ver.2 software. Standardized uptake value ratios (SUVRs) and distribution volume ratios (DVRs) by Logan reference tissue model (LRTM) were measured in eight brain regions using the cerebellar cortex as the reference. Blood tests, urine analysis, vital signs and electrocardiography were performed for safety assessments.

No adverse events were observed. The highest radiation doses were received by the gallbladder (257.7 ± 74.9 μGy/MBq) and the urinary bladder (127.3 ± 11.7 μGy/MBq). The effective dose was 26.8 ± 1.4 μSv/MBq. The parent form ([¹⁸F]MK-6240) was metabolized quickly and was less than 15% by 35 min post injection. While no obvious accumulation was found in the brain of healthy subjects, focal accumulation of [¹⁸F]MK-6240 was observed in the cerebral cortex of AD patients. Regional SUVRs of the focal lesions in AD patients increased gradually over time, and the difference of SUVRs between healthy subjects and AD patients became large and stable at 90 min after injection. High correlations of SUVR and DVR were observed (p < 0.01).

The findings supported safety and efficacy of [¹⁸F]MK-6240 as a tau PET tracer for Japanese populations. Even though the number of subjects was limited, the radiation dosimetry profiles, pharmacokinetics, and biodistribution of [¹⁸F]MK-6240 were consistent with those for non-Japanese populations.

Japan Pharmaceutical Information Center ID, JapicCTI-194972.