Detection of Voltage-Gated Potassium Channels 1.3 via Immuno-PET Visualizes Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory condition affecting approximately 1% of the global population, yet current diagnostic tools for early-stage RA lack sensitivity and fail to identify optimal treatment candidates. Voltage-gated potassium channel 1.3 (Kv1.3) plays a crucial role in immune cell activation, particularly in effector memory T lymphocytes and macrophages, which drive inflammation in active RA. This study aimed to develop and evaluate a novel Kv1.3-targeted radiopharmaceutical, [⁶⁸Ga]Ga-NOTA-anti-Kv1.3, for precise monitoring and quantification of joint inflammation in a mouse model of RA. PET imaging revealed significantly higher radioactivity concentration in inflamed joints compared to normal joints at all time points, with peak uptake of 11.73 %ID/g at 4 h postinjection compared to 1.55 %ID/g in noninflamed joints. Histological analysis confirmed the presence of T lymphocytes and macrophages in inflamed tissues and their high Kv1.3 expression. Additionally, tracer uptake correlated strongly with clinical arthritis scores (Pearson <i>r</i> = 0.8789, <i>p</i> < 0.0001), demonstrating the probe's sensitivity in tracking arthritis progression. This study successfully developed a ⁶⁸Ga-labeled Kv1.3-targeting radiopharmaceutical that enables visualization of active inflammation in arthritic joints, showing high sensitivity for early RA diagnosis and disease monitoring. This approach offers potential for guiding immune-targeted therapies and assessing the treatment efficacy in RA.