NESPS - Identifying Peripheral Nerve Injuries and Monitoring Axonal Regeneration by targeting the Colony Stimulating Factor 1 Receptor

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Identifying Peripheral Nerve Injuries and Monitoring Axonal Regeneration by targeting the Colony Stimulating Factor 1 Receptor
Jeffrey Khong^*¹, John Nguyen¹, Rachana Suresh¹, Zachary Zamore¹, Samarth Krishna¹, Mohammed Shahid¹, Jared Zhang¹, Alec Chen¹, Hyojin Cha², Andrew G. Horti², Will Padovano¹, Catherine Foss², Sami Tuffaha¹
¹Department of Plastic and Reconstructive Surgery, Johns Hopkins School of Medicine, Baltimore, MD; ²Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD

Background: Visualizing axonal regeneration along injured nerves is not possible with current imaging modalities, limiting diagnosis and management of peripheral nerve injuries. We sought to image macrophages and monocytes, which infiltrate damaged nerves, to non-invasively characterize nerve injury. We evaluated the use of the PET agent [¹⁸F]JHU1221683, which binds to the colony stimulating factor 1 receptor (CSF1R) expressed by proliferating macrophages, as a novel nerve imaging agent.

Methods: Sixteen male Lewis rats were divided into two groups: unilateral sciatic nerve transection with repair using a 3cm isograft or transection without repair, in which a 3cm isograft was coapted only to the distal stump. At 2- and 4- weeks post-intervention, animals received intravenous [¹⁸F]JHU1221683, and radioactivity was quantified with an automated gamma counter. To examine differential uptake, nerves were analyzed as 4 segments: proximal sciatic, proximal and distal graft, and distal sciatic. [¹⁸F]JHU1221683 uptake, expressed as percent injected dose per gram (%ID/gram), was compared between groups using Kruskal-Wallis and post-hoc Dunn tests.

Results: Relative to sham, sciatic nerves segments distal to the injury site from both unrepaired and repaired animals had significantly greater uptake at both 2 weeks (p<0.05) and 4 weeks (p<0.05). Uptake in both unrepaired and repaired nerve segments was significantly greater distal to injury site compared to segments proximal to the injury site (p<0.05). Compared to 2 weeks, uptake in distal segments at 4 weeks significantly decreased in repaired nerves (p<0.05) and remained constant in unrepaired nerves (p>0.05).

Conclusion: [¹⁸F]JHU1221683 effectively labeled macrophage content within injured nerves, with higher uptake observed in distal versus proximal segments, and in unrepaired nerves versus repaired nerves. These findings suggest that [¹⁸F]JHU1221683 PET imaging of CSF1R may be a promising non-invasive approach for the identification of peripheral nerve injuries and the monitoring of axonal regeneration following repair.

Figure 1. [18F]JHU1221683 uptake after sciatic nerve injury. (A) and (B) In both 2- and 4-week cohorts and in both repaired and unrepaired nerves, increased uptake was observed in segments distal to the site of injury relative to sham and proximal segments. (B) At 4 weeks, repaired nerves demonstrated decreased uptake in the distal sciatic segments compared to unrepaired nerves. (C) In repaired nerves, decreased uptake was observed by 4 weeks compared to 2 weeks in segments distal to the site of injury. (D) In unrepaired nerves, decreased uptake was observed in the proximal graft segments between 2 and 4 weeks. Uptake remained constant between 2 and 4 weeks in the distal graft and distal sciatic segments.

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