Background: Amino acid transporters, such as LAT1, are overexpressed in aggressive
prostate and breast carcinomas, directly influencing pathways of growth and proliferation.
Objective: The purpose of this study was to synthesize and characterize a novel 18F labeled leucine
analog, 5-[18F]fluoroleucine, as a potential imaging agent for aggressive tumors which may not be
amenable to imaging by FDG PET.
Methods: 5-fluoroleucine was synthesized and characterized, and its 18F-labeled analog was synthesized
from a mesylate precursor. First, breast cancer cell line assays were performed to evaluate uptake
of 3H- or 14C-labeled L-leucine and other essential amino acids. Both L-leucine and 5-
[18F]fluoroleucine were tested for uptake and accumulation over time, and for uptake via LAT1. Biodistribution
studies were performed to estimate radiation dosimetry for human studies. Small animal
PET / CT studies of a breast cancer were performed to evaluate in vivo 5-[18F]fluoroleucine tumor
Results: Breast cancer cell lines showed increasing high net accumulation of L-[14C]leucine. Both
L-leucine and 5-[18F]fluoroleucine showed increasing uptake over time in in vitro tumor cell assays,
and uptake was also shown to occur via LAT1. The biodistribution study of 5-[18F]fluoroleucine
showed rapid renal excretion, no significant in vivo metabolism, and acceptable dosimetry for use in
humans. In vivo small animal PET / CT imaging of a breast cancer xenograft showed uptake of 5-
[18F]fluoroleucine in the tumor, which progressively increased over time.
Conclusion: 5-[18F]fluoroleucine is a leucine analog which may be useful in identifying tumors with
high or upregulated expression of amino acid transporters, providing additional information that may
not be provided by FDG PET.