Successful treatment of chronic knee pain following localization by a sigma-1 receptor radioligand and PET/MRI: a case report

Abstract

Background: The ability to accurately diagnose and objectively localize pain generators in chronic pain sufferers remains a major clinical challenge since assessment relies on subjective patient complaints and relatively non-specific diagnostic tools. Developments in clinical molecular imaging, including advances in imaging technology and radiotracer design, have afforded the opportunity to identify tissues involved in pain generation based on their pro-nociceptive condition. The sigma-1 receptor (S1R) is a pro-nociceptive receptor upregulated in painful, inflamed tissues, and it can be imaged using the highly specific radioligand 18F-FTC-146 with PET.

Case presentation: A 50-year-old woman with a 7-year history of refractory, left-knee pain of unknown origin was referred to our pain management team. Over the past several years, she had undergone multiple treatments, including a lateral retinacular release, radiofrequency ablation of a peripheral nerve, and physical therapy. While certain treatments provided partial relief, her pain would inevitably return to its original state. Using simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) with the novel radiotracer 18F-FTC-146, imaging showed increased focal uptake of 18F-FTC-146 in the intercondylar notch, corresponding to an irregular but equivocal lesion identified in the simultaneously acquired MRI. These imaging results prompted surgical removal of the lesion, which upon resection was identified as an inflamed, intraarticular synovial lipoma. Removal of the lesion relieved the patient's pain, and to date the pain has not recurred.

Conclusion: We present a case of chronic, debilitating knee pain that resolved with surgery following identification of the pathology with a novel clinical molecular imaging approach that detects chronic pain generators at the molecular and cellular level. This approach has the potential to identify and localize pain-associated pathology in a variety of chronic pain syndromes.

Keywords: 18F-FTC-146; PET/MRI; chronic pain; intraarticular synovial lipoma; knee pain; molecular imaging; sigma-1 receptor.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1

PET/MRI and MRI of the left knee Notes: Axial (A) and coronal (B) PET/MRI show high uptake of 18F-FTC-146 in the intercondylar notch (red arrows: maximum standardized uptake value = 2.04). By comparison, the intercondylar notch of the right knee is normal (white arrow: maximum standardized uptake value = 0.17). MRI shows small joint effusion, with no synovitis, and an amorphous, mass-like in the intercondylar notch, initially presumed to be a ganglion cyst or localized pigmented villonodular synovitis/fibrous lesion. Sagittal (C) and coronal (D) MRI (T2-weighted with fat saturation) of the left knee, acquired approximately 3 years before PET/MRI study, show abnormal high-signal amorphous, mass-like but equivocal lesion in the intercondylar notch (white arrows). This had been overlooked or regarded as clinically insignificant.

Figure 2

Hematoxylin and eosinstain section of the left-knee mass Notes: The mass (pale tan tissue measuring 0.4 × 0.4 × 0.1 cm) was biopsied anteriorly from between the anterior cruciate ligament and the posterior cruciate ligament. This was one of three masses removed during knee arthroscopy, synovial biopsy, and synovectomy. The section shows mature adipose cells with overlying synovial lining. The infiltration and presence of inflammatory cells in this specimen is consistent with an inflamed synovial lipoma.