Radiosynthesis of a novel carbon-11-labeled ruxolitinib analogue and preliminary evaluation of its biodistribution via different routes of administration

Introduction. Ruxolitinib is a selective inhibitor of Janus kinases 1 and 2, suppressing JAK/STAT-dependent signaling involved in inflammation, immune response, and cell proliferation. In addition to systemic use, inhalation administration is of interest, potentially increasing local lung exposure and reducing systemic exposure. This study aimed to develop a method for radioisotope labeling of ruxolitinib with carbon-11 to investigate its biodistribution via different administration routes.
Materials and Methods. N-[¹¹C]-methylruxolitinib was obtained by a one-step methylation reaction of ruxolitinib using a fully automated, home-made module. The product was purified by solid-phase extraction, and radiochemical purity and identity were confirmed by radio- HPLC. Biodistribution was studied ex vivo in healthy male Wistar rats after intravenous and inhalation administration of the radioligand. Radioactivity accumulation in organs was assessed at 5, 10, 40, 60, and 80 minutes after administration.
Results. N-[¹¹C]-methylruxolitinib was obtained with a radiochemical yield of 40 % (when calculated as [¹¹C]CH3I), a radiochemical purity of ≥97 %, and a molar activity of 6‒10 GBq/μmol. A pilot study found that with inhalation administration, a tendency toward higher radioligand accumulation in the lungs was observed 5 minutes after administration compared to intravenous administration. In contrast, with intravenous administration, a tendency toward higher accumulation in the liver was observed at the same time point. However, by the 10^th minute, significant differences in biodistribution between the two routes of administration had disappeared.
Conclusions. In this study, the radiosynthesis of the N-[¹¹C]-methylated analogue of ruxolitinib is described for the first time, and a comparative assessment of its biodistribution by systemic and inhalation routes of administration is conducted.

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