PET Imaging of Denervation-Induced Muscle Cell Death with 18F-ML-10, a Novel Apoptosis Tracer (P07.198)

Abstract

Objective: Molecular imaging of denervation-induced myocyte apoptosis by 18 F-ML-10 PET. Background Muscle denervation is common in numerous neurological disorders, ranging from injuries to peripheral nerves to motor neuron disease. Currently, denervation is diagnosed by EMG and/or muscle biopsy, both invasive and limited in spatial information. Molecular imaging tool for denervation injury is therefore much needed. Since apoptosis has been shown to be an important mechanism in denervation-induced myocyte cell-death, we hypothesized that 18 F-ML-10, a PET tracer of apoptosis, may be useful for the respective clinical indications. Design/Methods: In a proof-of-concept study, denervation injury was induced by transection of the left sciatic nerve in rats. Animals were subjected to 18 F-ML-10 PET/CT scans at 24h, 3 and 7 days post-transection. Tracer uptake in muscles innervated by the sciatic nerve was compared to the uptake in contralateral muscles. Neurological deficits were followed from time of nerve transection to last 18 F-ML-10 scan, and assessed for correlation with tracer uptake in the target muscles. Results: Unilateral increase in 18 F-ML-10 uptake were observed specifically in the left hamstring muscles in all rats during the assessed time window, with generation of respective “hot spots” in the affected muscles. Substantially lower activity was measured in the muscles not exclusively innervated by the transected sciatic nerve. Uptake was highest at 24h after denervation, concurrent with the apoptotic peak, and decreased by 7 days post-surgery. Neurological deficits were well-correlated with the increased tracer uptake. Conclusions: This study provides the first application of apoptosis imaging with PET for a neuromuscular disorder. This study revealed “hot spots” generated by 18 F-ML-10, selectively at the site of the denervated muscles. Striving to advance diagnosis of motor neuron disease, and pending on further research, molecular imaging with 18 F-ML-10 may serve as a useful tool for “virtual biopsy”, i.e., non-invasive, integrative detection of muscle denervative processes. Supported by: Financially supported by Aposense Ltd. Disclosure: Dr. Reshef has received personal compensation for activities with Aposense Ltd as an employee. Dr. Ben-Ami has received personal compensation for activities with Aposense Ltd as an employee. Dr. Freedman has nothing to disclose. Dr. Davidson has received personal compensation for activities with Aposense Ltd as an employee. Dr. Mishani has nothing to disclose. Dr. Ziv has received personal compensation for activities with Aposense Ltd as an employee.