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Current Radiopharmaceuticals

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ISSN (Print): 1874-4710
ISSN (Online): 1874-4729

Research Article

Synthesis and Preliminary Evaluation of 5-[18F]fluoroleucine

Author(s): Bennett B. Chin, Darryl McDougald, Douglas H. Weitzel, Thomas Hawk, Robert E. Reiman, Michael R. Zalutsky and Ganesan Vaidyanathan

Volume 10, Issue 1, 2017

Page: [41 - 50] Pages: 10

DOI: 10.2174/1874471009666161230114954

Price: $65

Abstract

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 uptake.

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.

Keywords: Leucine, fluoroleucine, amino acid, tumor imaging, positron emission tomography, dosimetry.

Graphical Abstract

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