Evaluation of [¹⁸F]Mefway biodistribution based on whole-body microPET imaging of mice

Objectives [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 microPET studies in mice to evaluate the biodistribution and dosimetry of [¹⁸F]Mefway.

Methods Six mice (3 females, ~ 25g, 3 males, ~30g) received iv tail injections (9.48 ± 2.88 MBq) of [¹⁸F]Mefway and scanned for 2 hours in an Inveon dedicated PET scanner. Each animal also received an high resolution CT scan using an Inveon CT. The CT images were used to draw volume of interest (VOI) on the following organs: brain, large intestine, stomach, heart, kidneys, liver, lungs, pancreas, bone, spleen, testes, thymus and urinary bladder. All organ time activity curves had the decay correction reversed and were normalized to the injected activity. The portion of each curve between end of the scan and infinity was approximated with an exponential. 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 residence times in mouse organs were converted to human values using scale factors based on differences between organ and body weights. OLINDA 1.1 software was used to compute the absorbed dose in each organ.

Results The average mouse doses were 6.14E+01 mSv/MBq (urinary bladder), 3.18E+01 mSv/MBq (kidney), 2.79E+01 mSv/MBq (osteogenic cells) and less than 7.84E+00 mSv/MBq in other organs. The average human equivalent doses were 3.5E-02 mSv/MBq (urinary bladder), 3.1E-02 mSv/MBq (kidney), 2.47E-02 mSv/MBq (osteogenic cells) and less than 1.7E-02 mSv/MBq in other organs. The dose values correlated with those of ¹¹C-WAY , another 5-HT1A tracer for which dosimetry has been evaluated in humans.

Conclusions The elimination of radiotracer was primarily via kidney and urinary bladder with the urinary bladder being the critical organ. Whole-body mouse imaging can be used as a preclinical tool to estimate the absorbed doses of [18F]Mefway in humans.

Research Support NIH R21 AG03052