Skip to Main content Skip to Navigation
Journal articles

Effect of α-Methyl versus α-Hydrogen Substitution on Brain Availability and Tumor Imaging Properties of Heptanoic [F-18]Fluoroalkyl Amino Acids for Positron Emission Tomography (PET).

Abstract : Two [(18)F]fluoroalkyl substituted amino acids differing only by the presence or absence of a methyl group on the α-carbon, (S)-2-amino-7-[(18)F]fluoro-2-methylheptanoic acid ((S)-[(18)F]FAMHep, (S)-[(18)F]14) and (S)-2-amino-7-[(18)F]fluoroheptanoic acid ((S)-[(18)F]FAHep, (S)-[(18)F]15), were developed for brain tumor imaging and compared to the well-established system L amino acid tracer, O-(2-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET), in the delayed brain tumor (DBT) mouse model of high-grade glioma. Cell uptake, biodistribution, and PET/CT imaging studies showed differences in amino acid transport of these tracer by DBT cells. Recognition of (S)-[(18)F]15 but not (S)-[(18)F]14 by system L amino acid transporters led to approximately 8-10-fold higher uptake of the α-hydrogen substituted analogue (S)-[(18)F]15 in normal brain. (S)-[(18)F]15 had imaging properties similar to those of (S)-[(18)F]FET in the DBT tumor model while (S)-[(18)F]14 afforded higher tumor to brain ratios due to much lower uptake by normal brain. These results have important implications for the future development of α-alkyl and α,α-dialkyl substituted amino acids for brain tumor imaging.
Document type :
Journal articles
Complete list of metadatas

https://hal-amu.archives-ouvertes.fr/hal-01456936
Contributor : Françoise Dignat-George <>
Submitted on : Monday, February 6, 2017 - 10:17:34 AM
Last modification on : Wednesday, August 19, 2020 - 12:08:12 PM

Links full text

Identifiers

Collections

Citation

Ahlem Bouhlel, Wadha Alyami, Aixiao Li, Liya Yuan, Keith Rich, et al.. Effect of α-Methyl versus α-Hydrogen Substitution on Brain Availability and Tumor Imaging Properties of Heptanoic [F-18]Fluoroalkyl Amino Acids for Positron Emission Tomography (PET).. Journal of Medicinal Chemistry, American Chemical Society, 2016, 59, pp.3515-31. ⟨10.1021/acs.jmedchem.6b00189⟩. ⟨hal-01456936⟩

Share

Metrics

Record views

139