RT Journal Article
SR Electronic
T1 Radiosynthesis of Kappa Opioid Receptor Radioligand [<sup>11</sup>C]LY2795050, via In-loop [<sup>11</sup>C]Carbonylation Chemistry
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1454
OP 1454
VO 62
IS supplement 1
A1 Tanpreet Kaur
A1 Peter Scott
A1 Xia Shao
YR 2021
UL http://jnm.snmjournals.org/content/62/supplement_1/1454.abstract
AB 1454Objectives: KOR antagonist [11C]LY2795050 is the preferred radiotracer for PET imaging of kappa receptors owing to its high affinity (in vitro Ki = 0.72 nM; in vivo Kd = 0.028 nM) and good selectivity (μ/κ = 11; δ/κ = 132). [11C]LY2795050 was previously synthesized by our group in 2 steps [1]. The objective of the present study was to develop an improved route for the synthesis of [11C]LY2795050 [2] through [11C]CO insertion chemistry. Methods: Carbon-11 was produced via 14N(p,α)11C nuclear reaction to generate [11C]CO2 which was trapped on a molecular sieve column at room temperature. The accumulated [11C]CO2 was released into a controlled stream of helium (50 ml/min) while heating the molecular sieve trap to 360°C. The [11C]CO2 was passed through a heated molybdenum column (850 oC) to produce [11C]CO. [11C]CO was concentrated in a silica trap immersed in liquid nitrogen (‐196°C) and then released in a stream of Helium (3 mL/min) into a stainless steel HPLC loop pre-loaded with a mixture of all reactants. The loop was sealed for 5 min at room temperature for the 11C‐carbonylation reaction. Results: The synthesis was attempted using Pd2[π‐cinnamyl]Cl2, xantphos and iodoprecursor 1 by dissolving in anhydrous THF and then completely drying with a stream of nitrogen. 200 μL of THF and NH3 (0.5 M in THF) was added and the resulting mixture was introduced into the HPLC loop approximately 2 min prior to start of synthesis. This method resulted in the synthesis of [11C]LY2795050 in near quantitative yields. Conclusions: The present method provided a simple approach to synthesize [11C]LY2795050 in one pot and near quantitative yield. Further optimizations to automate the synthesis of [11C]LY2795050 for clinical use are in progress and will be reported in due course. References: [1] L. Yang, A. F. Brooks, K. J. Makaravage, H. Zhang, M. S. Sanford, Peter J. H. Scott, X. Shao, ACS Med. Chem. Lett. 2018, 9, 1274-1279.[2] M. Ferrat, K. Dahl, C. Halldin, M. Schou, J Label Compd Radiopharm. 2020, 63, 100-107.