AHLEM BOUHLEL, Presenter: Nothing to Disclose

Dong Zhou, Abstract Co-Author: Nothing to Disclose

AIXIAO LI, Abstract Co-Author: Nothing to Disclose

Liya Yuan MD, Abstract Co-Author: Nothing to Disclose

Keith M. Rich MD, Abstract Co-Author: Nothing to Disclose

Jonathan Edward McConathy MD, PhD, Abstract Co-Author: Speakers Bureau, Eli Lilly and Company Research Consultant, Eli Lilly and Company Research Consultant, General Electric Company Research Consultant, Blue Earth Diagnostics Ltd Research Consultant, Siemens AG

Radiolabeled amino acids (AAs) that cross the blood-brain barrier (BBB) through system L transport and are also concentrated and retained in tumors through system A transport may have improved imaging properties over existing system L tracers for brain tumors such as [18F]FDOPA and [18F]FET. The objective of this project is to develop 18F-labeled analogues of these AAs with longer alkyl chain with the optimal balance of transport by system A and system L.

Efficient organic and radiosynthetic routes were developed to obtain the target compound, (S)-2-amino-5-[18F]fluoro-2-methylpentanoic acid ((S)-[18F]FAMPe). The 18F incorporation was successfully performed in t-amyl alcohol to afford intermediate in 79 % yield, determined by radio-TLC and HPLC. Then, after a high yield purification by a C-18 HPLC column, a quantitatively deprotection and a Dionex OnGuard II A cartridge treatment, ((S)-[18F]FAMPe was obtained in 24% decay corrected yield and over 99% radiochemical purity in a form suitable for animal studies. Biodistribution studies were conducted in male BALB/c mice with subcutaneous DBT gliomas at 5, 30 and 60 min after injection (n= 5).

The new tracer demonstrate high uptake in DBT tumors (7.37 %ID/g at 30 min and 9.88 %ID/g at 60 min) with progressive increase over time. Uptake of activity in the brain was greater than the system A substrate (R)-[18F]MeFAMP but lower than the system L substrate [18F]FET. Tumor to brain ratios for (S)-[18F]FAMPe ranged from 8 to 12 which are lower than those obtained with (R)-[18F]MeFAMP but higher than with [18F]FET. These in vivo data combined with in vitro cell uptake assays suggest combined transport of (S)-[18F]FAMPe by system A and system L.

A novel non-natural 18F-labeled amino acid, (S)-[18F]FAMPe has been facilely prepared in good yields. Biodistribution results suggest that mixed system A/system L substrates can provide relatively high tumor to brain ratios while still being able to cross the BBB. Future efforts include the development of analogues of (S)-[18F]FAMPe and assessment of their imaging properties through small animal PET studies.

18F-labeled amino acids that target system A and system L transporters have the potential to provide superior brain tumor visualization compared to PET tracers targeting system L transport.

BOUHLEL, A, Zhou, D, LI, A, Yuan, L, Rich, K, McConathy, J, Radiosynthesis and Biological Evaluation of a Novel 18F-labeled α,α-disubstituted Amino Acid for Brain Tumor Imaging [ MI Scavenger Hunt! ].  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14045565.html