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Boramino acid as a marker for amino acid transporters.

Liu Z, Chen H, Chen K, Shao Y, Kiesewetter DO, Niu G, Chen X - Sci Adv (2015)

Bottom Line: Abnormal expression of AATs is often associated with cancer, addiction, and multiple mental diseases.The structure of a BAA is identical to that of the corresponding natural AA, except for an exotic replacement of the carboxylate with -BF3 (-).Cellular studies demonstrate strong AAT-mediated cell uptake, and animal studies show high tumor-specific accumulation, suggesting that BAAs hold great promise for the development of new imaging probes and smart AAT-targeting drugs.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (NIH), Bethesda, MD 20892, USA.

ABSTRACT
Amino acid transporters (AATs) are a series of integral channels for uphill cellular uptake of nutrients and neurotransmitters. Abnormal expression of AATs is often associated with cancer, addiction, and multiple mental diseases. Although methods to evaluate in vivo expression of AATs would be highly useful, efforts to develop them have been hampered by a lack of appropriate tracers. We describe a new class of AA mimics-boramino acids (BAAs)-that can serve as general imaging probes for AATs. The structure of a BAA is identical to that of the corresponding natural AA, except for an exotic replacement of the carboxylate with -BF3 (-). Cellular studies demonstrate strong AAT-mediated cell uptake, and animal studies show high tumor-specific accumulation, suggesting that BAAs hold great promise for the development of new imaging probes and smart AAT-targeting drugs.

No MeSH data available.


Related in: MedlinePlus

BAA is an AA mimic by substituting carboxylate group with its isosteric trifluoroborate.
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Figure 1: BAA is an AA mimic by substituting carboxylate group with its isosteric trifluoroborate.

Mentions: To meet all of these challenges, we substituted the carboxylate group (-COO−) with its isosteric trifluoroborate (-BF3−) (Fig. 1), which is not metabolized in vivo and can be readily labeled with 18F-fluoride through the recently established 18F-19F isotope exchange technology (20). Coincidentally, the in vivo stability of trifluoroborate moiety, which is poor in general, has been substantially enhanced by the adjacent ammonium group (table S2) (21). This design generates an entirely new type of chemicals, denoted as boramino acids (BAAs). Here, four representative BAAs have been synthesized and tested by computational modeling, cellular uptake assays, and in vivo biological evaluations. As expected, 18F-BAAs exhibited strong AAT-mediated transportation with high specificity. In addition, 18F-BAAs demonstrated distinctly high AAT-mediated tumor uptake and rapid clearance from normal organs and tissues. Notably, the uptake of 18F-BAAs in inflammatory regions is almost negligible, suggesting a unique advantage over 18F-fluorodeoxylglucose (FDG), which is now the gold standard PET tracer for clinical diagnosis.


Boramino acid as a marker for amino acid transporters.

Liu Z, Chen H, Chen K, Shao Y, Kiesewetter DO, Niu G, Chen X - Sci Adv (2015)

BAA is an AA mimic by substituting carboxylate group with its isosteric trifluoroborate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643766&req=5

Figure 1: BAA is an AA mimic by substituting carboxylate group with its isosteric trifluoroborate.
Mentions: To meet all of these challenges, we substituted the carboxylate group (-COO−) with its isosteric trifluoroborate (-BF3−) (Fig. 1), which is not metabolized in vivo and can be readily labeled with 18F-fluoride through the recently established 18F-19F isotope exchange technology (20). Coincidentally, the in vivo stability of trifluoroborate moiety, which is poor in general, has been substantially enhanced by the adjacent ammonium group (table S2) (21). This design generates an entirely new type of chemicals, denoted as boramino acids (BAAs). Here, four representative BAAs have been synthesized and tested by computational modeling, cellular uptake assays, and in vivo biological evaluations. As expected, 18F-BAAs exhibited strong AAT-mediated transportation with high specificity. In addition, 18F-BAAs demonstrated distinctly high AAT-mediated tumor uptake and rapid clearance from normal organs and tissues. Notably, the uptake of 18F-BAAs in inflammatory regions is almost negligible, suggesting a unique advantage over 18F-fluorodeoxylglucose (FDG), which is now the gold standard PET tracer for clinical diagnosis.

Bottom Line: Abnormal expression of AATs is often associated with cancer, addiction, and multiple mental diseases.The structure of a BAA is identical to that of the corresponding natural AA, except for an exotic replacement of the carboxylate with -BF3 (-).Cellular studies demonstrate strong AAT-mediated cell uptake, and animal studies show high tumor-specific accumulation, suggesting that BAAs hold great promise for the development of new imaging probes and smart AAT-targeting drugs.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (NIH), Bethesda, MD 20892, USA.

ABSTRACT
Amino acid transporters (AATs) are a series of integral channels for uphill cellular uptake of nutrients and neurotransmitters. Abnormal expression of AATs is often associated with cancer, addiction, and multiple mental diseases. Although methods to evaluate in vivo expression of AATs would be highly useful, efforts to develop them have been hampered by a lack of appropriate tracers. We describe a new class of AA mimics-boramino acids (BAAs)-that can serve as general imaging probes for AATs. The structure of a BAA is identical to that of the corresponding natural AA, except for an exotic replacement of the carboxylate with -BF3 (-). Cellular studies demonstrate strong AAT-mediated cell uptake, and animal studies show high tumor-specific accumulation, suggesting that BAAs hold great promise for the development of new imaging probes and smart AAT-targeting drugs.

No MeSH data available.


Related in: MedlinePlus