Radiation dose estimates for [18F]5-fluorouracil derived from PET-based and tissue-based methods in rats

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Dosimetry
• Small Animal Imaging

Background:

• Radiation dosimetry is crucial for pharmaceutical biodistribution assessment.
• Traditional rodent dosimetry relies on ex vivo radioassay of harvested organs.
• Small-animal PET offers a novel alternative for in vivo dosimetry.

Purpose of the Study:

• To compare radiation dose estimates derived from small-animal PET imaging versus traditional tissue harvesting.
• To assess the biodistribution of the 18F-labeled chemotherapy agent [18F]5-fluorouracil ([18F]5-FU) in rats.
• To extrapolate rodent data for human absorbed dose calculations.

Main Methods:

• Dynamic small-animal PET data acquired for up to 2 hours post-injection of [18F]5-FU in rats (n=16).
• Time-activity data modeled using combined polynomial and exponential functions.
• Extrapolation of rodent data to human organs for absorbed dose calculation.

Main Results:

• High correlation (r>0.999) between imaging-based and harvesting-based organ activities.
• Highly correlated human dosimetry estimates (r=0.998) across methods.
• Highest radiation doses estimated in organs related to excretion (bladder wall, liver, intestines).
• Effective dose (ED) of 2.94E-2 mSv/MBq (harvesting) and 2.97E-2 mSv/MBq (PET).

Conclusions:

• Small-animal PET provides radiation dose estimates with statistical and logistical advantages.
• PET imaging is a viable alternative to traditional tissue harvesting for rodent dosimetry.
• This method facilitates more efficient radiopharmaceutical dosimetry studies.