S1R PET/MRI of patients with chronic knee pain reveals potential pain generators not otherwise identified with standard care: Early experience. (2021)

143 Objectives: Chronic knee pain is a common medical condition affecting approximately 25% of adults, and the diagnosis of knee pain remains a challenge since conventional diagnostic methods, such as MRI, can be inaccurate or misleading. A new method, which utilizes the sigma-1 receptor (S1R) radioligand, [18F]FTC-146, has emerged as a potentially more accurate way to image pain generators. Sigma-1 receptor, a receptor whose expression is increased in painful and inflamed tissues, modulates a variety of ion channels involved in nociception and cell signaling. Tracking this receptor through PET imaging thus allows identification of pain Making it This study investigates the use of this radiotracer in conjunction with positron emission tomography/magnetic resonance imaging (PET/MRI) in diagnosing the etiology of chronic knee pain. Methods: This IRB approved study identified 10 patients with chronic knee pain duration > 6-month and pain level > 4/10) who had failed standard medical and surgical management. Patients underwent whole body S1R TOF PET/3.0T MRI. Maximum standard uptake values (SUVmax) of the radiotracer were measured and target to background (TTB) ratios were determined and compared with the means of 9 whole-body S1R PET/MRIs of asymptomatic control (AC) subjects. Single sample Z-score test was used to compare between an individual TTB ratio from a pain patient against the mean TTB and standard deviation (SD) obtained from the same location in our AC cohort. Significance is >1.96 (95% confidence level). The 10 patients’ knee MRIs were separately analyzed for MR abnormalities such as the presence of meniscal tears, joint effusion, osteoarthritis, etc. The patient’s outcomes of the patients were followed via their electronic medical record. Results: S1R PET showed that all 10 knee pain patients showed statistically significant, abnormally increased uptake of S1R radioligand compared to AC in a variety of locations, categorized as joint, bone, muscle and other as described in (Table 1). In contrast, MRIs showed four patients with no MR abnormalities, 3 with expected post-surgical changes on MRI that were felt unrelated to the patients’ pain and 3 with MRI findings consistent with osteoarthritis and/or meniscal tear (Table 2). Among the 6 cases that showed changes on MRI, only 3 cases showed an associated abnormal increase in radiotracer uptake at the site of PET abnormality. Additionally, at sites of abnormal PET uptake, MRI often did not demonstrate abnormalities, most notably in the bones and muscles. Limited clinical follow up showed a subset of patients benefiting from guidance per the PET/MRI result: one patient with surgical resection of the synovial mass and resolution of pain, one patient with total knee replacement due to refractory pain, and two patients with synovectomy and removal of adhesions, resulting in cessation of pain. Conclusion: In this preliminary study, patients with chronic knee pain demonstrated areas of abnormally increased S1R radioligand uptake in the joint, bone, muscle or others compared to asymptomatic control patients. PET detected abnormalities in all patients, while MRI detected abnormalities in about half of the patients. S1R-PET/MR can potentially help inform clinical decision making with respect to surgery or other treatment options by revealing abnormalities in the areas that are not apparent by MR imaging alone.