Biodistribution and Radiation Dosimetry of C-11 Nicotine derived from studies performed in humans.

500 Objectives The objective of this study is to determine the distribution and clearance pattern of C-11 Nicotine in humans and to estimate the radiation dosimetry of C-11 Nicotine. Methods Whole body PET/CT images were acquired in eleven healthy control subjects (5 males and 6 females) after intravenous (i.v.) administration of 505 ± 96 MBq (13.6 ± 2.6 mCi) of C-11 Nicotine. The scans were acquired in 3D mode over a two hour period post injection for a total of fourteen frames. Low dose CT scans of the brain and the whole body were acquired for attenuation correction purposes followed by the PET scan. Prior to the whole body PET scans, dynamic brain scans were acquired (45 frames, 2 sec each). Subsequently, 12 whole body image sets (head to mid-thigh) were obtained using the following image sequence: 2 x 15 sec, 3 x 20 sec, 2 x 30 sec, 3 x 60 sec, and 2 x 90 sec. A final image set was acquired to include the top of the head to the toes (60 sec/bed frame). Regions of interest (ROIs) were drawn on organs well delineated on the PET scans. The time activity curves (TACs) were generated to study the distribution and retention pattern of C-11 Nicotine. Residence times of C-11 Nicotine in various organs were then calculated from the TACs. The MIRD method was used to estimate the radiation exposure of select organs and the body as a whole. Results C-11 Nicotine was well tolerated by the research subjects and no pharmacological response was noted during the 2 hour PET/CT imaging session. After an initial distribution of C-11 Nicotine, the brain, lungs, liver and kidneys were clearly delineated on early images (figure 1, 2.8 min) and the urinary bladder was visible on the late images (figure 1, 23 min). Dynamic brain images show a steady rise of radioactivity in the brain during the 90 sec scan. Slightly higher uptake in the brain was noted for females but these differences were statistically insignificant (p=0.15). The highest uptake of C-11 was noted in the muscles with 15.5%ID and 21.0%ID at 3 and 72 min, respectively. The %ID of C-11 in the liver, brain, bone marrow, and lungs was 10.29 ± 2.11, 6.78 ± 1.61, 5.52 ± 2.25, and 6.64 ± 2.46, respectively at 3 min and 10.79 ± 3.55, 2.21 ± 0.60, 6.01 ± 1.94 and 3.07 ± 0.71, respectively at 73 min. The mean residence times for the muscle, liver, bone marrow, brain, and lungs were 5.3, 2.9, 1.9, 1.3, and 1.2 min, respectively. Overall, a low radiation exposure was estimated for most organs. Majority of injected C-11 radioactivity was cleared from tissues via urinary excretion. Although, a slightly higher uptake was noted in the stomach, brain and urinary bladder of female subjects, these differences were statistically insignificant (p=0.3). Thereby, no gender differences were noted for radioactivity accumulation and excretion of C-11 Nicotine. The mean effective dose to select organs such as the lower large intestine, liver, lungs, bone-marrow, stomach wall and the urinary bladder wall was 0.83 ± 0.21, 0.45 ± 0.08, 0.75 ± 0.15, 0.62 ± 0.06, 0.72 ± 0.24, and 0.73 ± 0.44 µSv/MBq, respectively. The calculated mean effective dose for a 70 kg human is estimated to be 5.44 ± 0.66 µSv/MBq (20.11 ± 2.47 mrem/mCi); signifying a low radiation exposure from C-11 Nicotine administration. Conclusions A rapid distribution and clearance of C-11 Nicotine via urinary excretion was observed after i.v. administration of C-11 Nicotine. Overall, a low radiation absorbed dose to most organs was noted for the C-11 Nicotine, thus providing the opportunity to inject ~10 mCi of C-11 Nicotine/study and be able to perform up to 3-4 PET/CT studies in quick succession without exceeding the allowable radiation exposure limit to human subjects. $$graphic_A8EB94FA-54E4-4F5C-BF6F-12D59C380D19$$ $$graphic_0F10E9D7-C82C-47CA-9FE7-5483853CB13A$$ $$graphic_C94CDA88-9C3F-4A6D-907B-75653A5AA3B2$$ $$graphic_EB6B4195-8444-4144-8DC8-8E88F7B9D3F6$$