TY - JOUR T1 - <strong>Fully automated one-pot radiosynthesis and dosimetry estimation for (<em>R</em>)-[<sup>18</sup>F]MeFAMP, a system A amino acid transport imaging agent</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 519 LP - 519 VL - 61 IS - supplement 1 AU - Dattatray Devalankar AU - Norio Yasui AU - Sharon White AU - Jonathan McConathy Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/519.abstract N2 - 519Objectives: Establish an automated radiosynthesis method and estimate human dosimetry for the non-natural amino acid 3-[18F]fluoro-2-methyl-2-N-(methylamino)propanoic acid ([18F]MeFAMP) for PET imaging of system A amino acid transport. (R)-[18F]MeFAMP has shown promising results for imaging brain tumors and other malignancies in preclinical models.1-4 Methods: An efficient fully automated method for the radiosynthesis of enantiomerically pure (R)-[18F]MeFAMP has been developed using a TracerLab FXFN module via nucleophilic ring opening of a cyclic sulfamidate precursor with [18F]fluoride. The amino acid α-methyl-(N-methyl)-serine is the major side product in this reaction and was separated by semi-preparative HPLC on a Chirobiotic TAG column using 0.2% formic acid in H2O as mobile phase. The tissue distribution of radioactivity was measured in normal male Balb/c mice of age 9 to 10 weeks to provide an estimate of human radiation dosimetry. Groups of 4 or 5 mice were sacrificed post injection of (R)-[18F]MeFAMP at 1, 10, 15, 30, 60, and 120 min, respectively. Comparison of (R)-[18F]MeFAMP bio-distribution in male mice vs female mice has also been done at 30, 60 and 120 min post injection. Human dosimetry estimates were calculated using the program OLINDA. Results: [18F]MeFAMP was produced in 46-50% decay corrected radiochemical yield with radiochemical and enantiomeric purity of &gt;99% after 110 min of total radiosynthesis time including HPLC purification. The molar activity was &gt;37GBq/μmol at the end of synthesis. The biodistribution studies of [18F]MeFAMP demonstrated the highest concentrations of radioactivity in the kidneys and pancreas. Activity from these and other normal tissues decreased substantially by 120 min. The activity in the brain was lowest for all time points, consistent with lack of system A transport at the luminal side of the normal blood-brain barrier. Female mice had significantly less uptake in certain tissues including the blood, brain, myocardium, and skeletal muscle in female mice. [18F]MeFAMP uptake for female mice in blood and heart is 0.45 ± 0.07 and 2.36 ± 0.70 respectively at 30 min, whereas for male mice [18F]MeFAMP uptake in blood and heart is 1.58 ± 0.18 and 3.34 ± 0.95 respectively at 30 min. The estimated effective dose for [18F]MeFAMP is very similar to the glucose analogue [18F]FDG which is used routinely for clinical imaging. Conclusions: The automated radiosynthesis provides high and reproducible yields of [18F]MeFAMP suitable for routine production for human use. The estimated radiation dosimetry of this PET tracer is acceptable and similar to other 18F-labeled PET tracers. The uptake of this tracer differs in female versus male mice although the reason for these differences is not yet known. References: (1) McConathy, J.; et al. J. Med. Chem. 2002, 45, 2240; (2) Weiping Yu et al. J. Med. Chem. 2015, 53, 876; (3) Jiang, X. et al. Int J Radiat Oncol Biol Phys. 2014, 89, 714; (4) Jiang, X. et al. Clin Cancer Res. 2014, 20, 2695. ER -