Evaluation of [18F]Mefway Biodistribution and Dosimetry Based on Whole-Body PET Imaging of Mice

Abstract

Purpose [18F]Mefway is a novel radiotracer specific to the serotonin 5-HT1A receptor class. In preparation for using this tracer in humans, we have performed whole-body PET studies in mice to evaluate the biodistribution and dosimetry of [18F]Mefway. Methods Six mice (three females and three males) received IV injections of [18F]Mefway and were scanned for 2 h in an Inveon-dedicated PET scanner. Each animal also received a high-resolution CT scan using an Inveon CT. The CT images were used to draw volume of interest on the following organs: the brain, large intestine, stomach, heart, kidneys, liver, lungs, pancreas, bone, spleen, testes, thymus, gallbladder, uterus, and urinary bladder. All organ time-activity curves without decay correction were normalized to the injected activity. The area under the normalized curves was then used to compute the residence times in each organ. Data were analyzed using PMOD and Matlab software. The absorbed doses in mouse organs were computed using the RAdiation Dose Assessment Resource animal models for dose assessment. The residence times in mouse organs were converted to human values using scale factors based on differences between organ and body weights. OLINDA/EXM 1.1 software was used to compute the absorbed human doses in multiple organs for both female and male phantoms. Results The highest mouse residence times were found in the liver, urinary bladder, and kidneys. The largest doses in mice were found in the urinary bladder (critical organ), kidney, and liver for both females and males, indicating primary elimination via urinary system. The projected human effective doses were 1.21E–02 mSv/MBq for the adult female model and 1.13E–02 mSv/MBq for the adult male model. The estimated human biodistribution of [18F]Mefway was similar to that of [11C]WAY 100,635, a 5-HT1A tracer for which dosimetry has been evaluated in humans. Conclusions The elimination of radiotracer was primarily via the kidney and urinary bladder with the urinary bladder being the critical organ. Whole-body mouse imaging can be used as a preclinical tool to provide initial estimates of the absorbed doses of [18F]Mefway in humans.

Internal Dose Assessment of (–)-18F-Flubatine, Comparing Animal Model Datasets of Mice and Piglets with First-in-Human Results

“…At the end of the respective measurement, the values decreased significantly for the liver (mice, 0.05 6 0.02; piglets, 5.4 6 2.1; humans, 8.4 6 1.2) and kidneys (mice, 0.01 6 0.003; piglets, 1.4 6 0.3; humans, 1.4 6 0.3). These organs are the most highly exposed in all investigated species, with organ doses comparable to those of other 18 F-labeled tracers (e.g., 18 F-mefway, 18 F-nifene) (13,14) as well as to the 11 C-labeled 11 C-WAY (15). Figure 6 shows a summary of all ODs for the 3 investigated species.…”

Evaluation of [18F]Nifene biodistribution and dosimetry based on whole-body PET imaging of mice

“…(4)) showed that the effective doses calculated from rat data were overestimated compared to those measured in nonhuman primates [22]. On the other hand the results of our previous work [23] in which we extrapolated the mouse dosimetry of the 5-HT 1A tracer [ 18 F]Mefway to human suggested that the urinary organs (bladder and kidneys) doses derived from the mouse model were underestimated.…”

Biodistribution and Radiation Dosimetry of [18F]Mefway in Humans

“…Based on biodistribution data, the excretion for [ 18 F]Mefway were mainly through the gastrourinary tract because of the radioactivity preceding pattern from the kidney to the urinary bladder and the remarkable uptake in the urinary system compared with the digestive system. The estimated radiation dose of 40.23 μSv/MBq from the human subjects is 3.3 times larger than the previous preclinical prediction results from the mice (11.3 or 12.1 μSv/MBq) [17]. In addition, little uptake in the bone indicates that [ 18 F]Mefway has metabolic stability against in vivo defluorination in humans.…”