Evaluation of GCPII expression in a rat model of peripheral nerve injury - a new marker for more precise diagnosis and prognosis of peripheral nerve lesions

• Applicant: Dr. Johannes Heinzel
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 565478223

Currently, there are no reliable non-invasive methods to reliably differentiate between closed nerve injuries of varying severity (Sunderland II-IV). These injuries lead to denervation of the muscles supplied by the affected nerve, which regresses as spontaneous regeneration begins after the injury. A promising approach is PET imaging using the radiopharmaceutical 18F-DCFPyL, which visualizes the expression of the enzyme GCPII. However, this technique has so far only been studied in the most severe nerve injuries (Sunderland V). The aim of this project is to extend its application to Sunderland II-IV injuries and to translate the findings into clinical research. Objective 1: Evaluation of GCPII Expression in Nerve Injuries of Different Severity; The first step is to investigate whether 18F-DCFPyL can differentiate between varying degrees of nerve injury in a rat model of peripheral nerve injury. For this purpose, sciatic nerve lesions will be induced in Lewis rats, corresponding to Sunderland II (lesion with full spontaneous recovery), Sunderland III (lesion with often incomplete spontaneous recovery), and Sunderland IV (severe damage, no spontaneous recovery). Sunderland V lesions (complete nerve transection, no spontaneous recovery) and the uninjured contralateral extremity of the animals will serve as controls. One week after the injury, before spontaneous regeneration commences, muscle uptake of 18F-DCFPyL will be analyzed by ex vivo biodistribution studies and in vivo PET-MRI imaging. We aim to characterize the uptake and distribution of the radiopharmaceutical for the respective injury grades and to evaluate whether the method is suitable as a specific diagnostic tool. Objective 2: Correlation of GCPII Expression and Regeneration; The second step is to investigate how GCPII expression and the uptake of 18F-DCFPyL correlate with the functional regeneration of the muscles innervated by the injured sciatic nerve. Therefore, rats with sciatic nerve injuries of varying degrees (Sunderland II-IV) will be studied over the course of eight weeks. At two, four, and eight weeks postoperatively, PET-MRI imaging will be performed to assess 18F-DCFPyL uptake. Functional recovery of the muscle supplied by the sciatic nerve will be evaluated by means of the so-called Static Sciatic Index (SSI). The aim is to determine how long the 18F-DCFPyL uptake persists and how it correlates with spontaneous regeneration following peripheral nerve injuries of different severity. Goal and Significance: This project aims to develop a more precise method for diagnosing and assessing the progression of functional recovery following closed nerve injuries of different severities. These findings could then be translated to clinical trials and ultimately improve the care of patients with peripheral nerve injuries significantly.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Dr. Sami Tuffaha