Synthesis and preliminary evaluation of 5-[18F] fluoroleucine.
| dc.contributor.author | Chin, Bennett B | |
| dc.contributor.author | McDougald, Darryl | |
| dc.contributor.author | Weitzel, Douglas H | |
| dc.contributor.author | Hawk, Thomas | |
| dc.contributor.author | Reiman, Robert E | |
| dc.contributor.author | Zalutsky, Michael R | |
| dc.contributor.author | Vaidyanathan, Ganesan | |
| dc.coverage.spatial | United Arab Emirates | |
| dc.date.accessioned | 2017-02-01T23:04:07Z | |
| dc.date.available | 2017-02-01T23:04:07Z | |
| dc.date.issued | 2016-12-30 | |
| dc.description.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 is 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 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-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. | |
| dc.identifier | ||
| dc.identifier | CRP-EPUB-80683 | |
| dc.identifier.eissn | 1874-4729 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Bentham Science Publishers Ltd. | |
| dc.relation.ispartof | Curr Radiopharm | |
| dc.title | Synthesis and preliminary evaluation of 5-[18F] fluoroleucine. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Zalutsky, Michael R|0000-0002-5456-0324 | |
| duke.contributor.orcid | Vaidyanathan, Ganesan|0000-0003-3041-8275 | |
| pubs.author-url | ||
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | Radiation Oncology | |
| pubs.organisational-group | Radiology | |
| pubs.organisational-group | Radiology, Nuclear Medicine | |
| pubs.organisational-group | School of Medicine | |
| pubs.publication-status | Published online |
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