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

Objectives [¹⁸F]Nifene is a nicotinic α4β2 receptor tracer agonist (Ki = 0.50 nM) that is important to study tobacco dependence, and cognitive deficits in Alzheimer’s disease. To facilitate the use of this tracer in humans we have performed whole-body microPET studies in mice to evaluate the organ biodistribution and dosimmetry.

Methods Five mice (4 males, 1 female, ~25g each) received iv tail injections (7.53 ± 0.87 MBq) of [¹⁸F]Nifene 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 and small 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. The residence times in mouse organs were converted to human values using scale factors based on differences between organ and body weights of the two species. OLINDA 1.1 software was used to compute the absorbed dose in each organ.

Results The average mouse doses were 5.81E+02 mSv/MBq (urinary bladder), 4.50E+01 mSv/MBq (kidney), 4.05E+01 mSv/MBq (stomach wall), 2.63E+01 mSv/MBq (spleen), and less than 2.1E+01 mSv/MBq in other organs. The average human equivalent doses were 5.8E-02 mSv/MBq (urinary bladder), 2.64E-02 mSv/MBq (kidney), 1.98E-02 mSv/MBq (stomach wall), 1.59E-02 mSv/MBq (spleen), and less than 1.50E-02 mSv/MBq in other organs.

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

Research Support NIH R01 AG02947