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Synthesis and Preliminary Evaluation of 5-[18F]fluoroleucine.
- Source :
-
Current radiopharmaceuticals [Curr Radiopharm] 2017; Vol. 10 (1), pp. 41-50. - Publication Year :
- 2017
-
Abstract
- Background: Amino acid transporters, such as LAT1, are overexpressed in aggressive prostate and breast carcinomas, directly influencing pathways of growth and proliferation.<br />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.<br />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.<br />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.<br />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.<br /> (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Subjects :
- Animals
Breast Neoplasms diagnostic imaging
Cell Line, Tumor
Humans
Image Processing, Computer-Assisted
Mice
Mice, Inbred BALB C
Molecular Structure
Positron Emission Tomography Computed Tomography
Radiometry
Sensitivity and Specificity
Tissue Distribution
Breast Neoplasms radiotherapy
Fluorine Radioisotopes chemistry
Fluorine Radioisotopes pharmacology
Leucine analogs & derivatives
Leucine chemistry
Radiopharmaceuticals chemical synthesis
Radiopharmaceuticals pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1874-4729
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Current radiopharmaceuticals
- Publication Type :
- Academic Journal
- Accession number :
- 28034351
- Full Text :
- https://doi.org/10.2174/1874471009666161230114954