PT - JOURNAL ARTICLE AU - Austin Zhao AU - Allen Brooks AU - David Raffel AU - Peter Scott AU - Xia Shao TI - Fully Automated Radiosynthesis of [<sup>11</sup>C]Guanidines and Bioevaluation of [<sup>11</sup>C]PHPOG as Cardiac Imaging Agent DP - 2020 May 01 TA - Journal of Nuclear Medicine PG - 63--63 VI - 61 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/61/supplement_1/63.short 4100 - http://jnm.snmjournals.org/content/61/supplement_1/63.full SO - J Nucl Med2020 May 01; 61 AB - 63Introduction: Guanidine has been found in a variety of natural products1 and many guanidine synthesis methods have been investigated. However, radiosyntheses of guanidines remain challenging, especially using the short half-life isotope carbon-11. A manual method developed by Westerberg and Långström2 has been used for almost 30 years. We herein report an efficient and fully automated method for the preparation of [11C]guanidines using a commercially available radiosynthesis module, as well as preliminary PET imaging of [11C]-para-hydroxyphenoxyethylguanidine ([11C]PHPOG) as a cardiac imaging agent of sympathetic nerve density. Methods: Production of [11C]guanidines was carried out using a GE TracerLab FXm. Briefly, the hydrogen [11C]cyanide from the GE PETTrace cyclotron and process panel3 was passed through a pyridinium perbromide column to form [11C]cyanogen bromide, and bubbled into the reactor containing amine precursor in sodium borate (pH 8.0). The reaction mixture was then heated to 80 ℃ for 5 minutes to afford [11C]cyanamide intermediate (Figure 1), and then treated with 35% NH4Cl in NH4OH at 140 ℃ for 8 minutes to yield crude [11C]guanidine product. The mixture was purified by reverse-phase chromatography (Phenomenex Synergi HydroRP 250 x 10.00 mm) with 10% EtOH in 60 mM NH4OAc at a flow rate of 5.0 mL/min. Myocardial imaging was performed by dynamic MicroPET scanning for 60 minutes in New Zealand white rabbits. Results: [11C]Guanylation of nine substrates were studied. The synthesis conditions were optimized and fully automated. The highest radiochemical conversion required a high concentration of NH4Cl/NH4OH solution and increased pressurewith temperature of 140 °C for 8 minutes. Radiochemical conversions were 9-78% based on HPLC. Two of these compounds were purified and the final injectable doses reaches greater than 95% purity and 9-31% radiochemical yield. The preliminary microPET imaging showed good myocardial uptakes in rabbit hearts (Fig 1). Conclusions: We have developed a reliable and fully automated radiosynthesis method for carbon-11 guanylation of amines using commercially available radiosynthesis module. Evaluation of [11C]PHPOG in rabbit hearts show promise for further studies. References:[1] Guanidines Historical, Biological, Biochemical, and Clinical Aspects of the Naturally Occurring Guanidino Compounds; Mori, A., Cohen, B. D., Lowenthal, A., Eds.; Plenum Press: New York, 1985.[2] Westerberg, G.; Kärger, W.; Onoe, H.; Långström, B. [11C]Cyanogen Bromide in the Synthesis of 1,3-Di(2-tolyl)-[11C]guanidine. J. Labelled Compds. Radiopharm. 1994, 34, 691-696.[3] Shao, X.; Rodnick, M. E.; Brooks, A. F.; Scott, P. J. H. Synthesis and Applications of [11C]Hydrogen Cyanide. In Further Radiopharmaceuticals for Positron Emission Tomography and New Strategies for Their Production: Further Radiopharmaceuticals for Positron Emission Tomography and New Strategies for Their Production; Scott, P. J. H., Eds.; John Wiley &amp; Sons, Incorporated: New Jersey, 2015; pp 233-240.