Subjects

A total of 14 normal volunteers were enrolled in the present study. The subjects were divided into group A, which was studied through ¹¹C-DNP PET scan after the oral administration of DNP, and group B, which was evaluated by ¹¹C-DNP PET scan after no oral administration of DNP. Group A consisted of four females (mean age: 57.3±4.5 y), three of whom underwent ¹¹C-DNP PET scans twice. One PET scan was performed at 2.5 h after the oral intake of 1 mg of DNP and one at 2.5 h after the oral intake of 30 µg of DNP. In one subject, the study was performed only after 30 µg intake.

In the present study, we set the amount of DNP at 1 mg for the oral administration to reduce the probability of adverse effects in normal volunteers. This amount was 20% of the initially prescribed dose of DNP for therapy in clinical settings. No subject complained of the adverse effects after the oral administration of 1 mg of DNP.

The consensus guideline by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has approved less than 50% of the no-observed-adverse-effect level (NOAEL) in an exploratory clinical trial (11). Accordingly, DNP dose of 1 mg in the present study was within this range.

On the other hand, group B consisted of 10 normal volunteers (5 males and 5 females; mean age: 48.3±6.1 y). These subjects did not have any mental diseases and did not use any medicines regularly. The normality of their condition was checked by blood sampling, cranial magnetic resonance imaging, and electrocardiography. The whole-body dosimetry of ¹¹C-DNP was reported to be 2.7 mSv for 500 MBq of ¹¹C-DNP (6).

This study was approved by the Institutional Ethics Committee, and written informed consents were obtained from all the candidates.