Chaofeng Huang PhD, Presenter: 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: Research Consultant, Eli Lilly and Company Speakers Bureau, Eli Lilly and Company

The radiolabeled histidine analogue AFETP, with promising preclinical tumor imaging properties, is a substrate for cationic amino acid transport in vitro. To further develop this novel non-natural amino acid series for PET tumor imaging, we synthesized a novel AFETP analogue, (S)-2-amino-3-[1-(2-[18F]fluoroethyl)-1H-[1,2,3]triazol-4-yl]hexanoic acid (AFETH) and tested this new tracer through cell uptake and bio-distribution studies in a mouse model of high grade glioma.

Non-radioactive AFETH and its labeling precursor were prepared from an enantiomeric pure Schiff imine. (S)-[18F]AFETH was prepared through the click reaction between the amino acid alkyne precursor and 2-azido-1-[18F]fluoroethane, followed by acidic deprotection. The reaction mixture was neutralized with NaHCO3 followed by a chiral HPLC. Radiochemical yield and purity were measured with radiometric thin-layer chromatography (TLC) and HPLC. Bio-distribution studies with (S)-[18F]AFETH were performed in male BALB/c mice at 14 days after implantation of subcutaneous DBT tumor cells.

The click reaction provided (S)-[18F]AFETH in a total synthesis time of 95 min, with 30% end of synthesis yield, and specific activity > 0.8 Ci/μmole) as assessed by radiometric TLC and HPLC. The bio-distribution data demonstrated good tumor to brain ratio within 5 min of injection, persistent activity in the tumor, and tumor to brain ratios of over 11:1 at 60 min after injection. The absolute uptake and retention was not identical to the pattern observed with (S)-[18F]AFETP, suggesting differences in transport and retention mechanisms. The tumor to brain and tumor to muscle ratios with (S)-[18F]AFETH were appropriately 11:1, and 2:1, respectively, at 60 min after injection. The low brain uptake of this tracer may limit its ability to visualize non-enhancing regions within gliomas.

The novel PET tracer, (S)-[18F]AFETH, is readily labeled in high yield through click reaction. Bio-distribution studies in the mouse DBT model of glioma demonstrate good imaging properties. Further evaluation of this compound and structural analogues with increased blood-brain barrier penetration for brain tumor imaging is ongoing.

The novel tracer (S)-[18F]AFETH showed good tumor imaging properties in initial preclinical studies and has potential use for the evaluation of patients with primary and metastatic brain tumors.

Huang, C, Yuan, L, Rich, K, McConathy, J, Radiosynthesis and Evaluation of (S)-2-amino-3-[1-(2-[18F]fluoroethyl)-1H-[1,2,3]triazol-4-yl]hexanoic acid for Brain Tumor Imaging.  Radiological Society of North America 2012 Scientific Assembly and Annual Meeting, November 25 - November 30, 2012 ,Chicago IL. http://archive.rsna.org/2012/12029182.html