Final Report Summary - ILLUMINATING NERVES (Hybrid imaging agents for the illumination of peripheral nerve structures)
The aim of the ILLUMINATING NERVES project was to develop imaging technologies that eventually can be used for nerve sparing surgery. These efforts extend the contribution that the Interventional Molecular Imaging Laboratory (www.imageguidedsurgery.nl) has already made in the development of disease-targeted surgical guidance technologies. Extending surgical guidance with the (intraoperative)illumination of delicate anatomical structures helps create an environment wherein surgical outcome can be balanced with the quality of life of patients. The quest for such a balance creates a new window of opportunities for the chemical development of imaging agents for surgical guidance applications.
Following the creation of a comprehensive overview of the reported tracers for peripheral nerves we have set out to develop imaging solutions for somatic and autonomic nerves that have no affinity for the central nervous system (potential site of toxicity) and have a high nerve specificity. In doing so, we have created a number of different nerve specific imaging tracers. Some target specific biomarkers in the myelin sheath or the neuronal body, while others support nerve visualization via local migration along nerves bundles. By providing these complementary nerve-imaging solutions, we have been able to cover the full biological complexity of the peripheral nerve anatomy that needs to be spared during surgery. During these efforts, we realized (local) targeting of peripheral nerves, while preventing uptake of the agents by the central nervous system. Next to the development of effective targeting vectors, a good imaging tracer relies heavily on the integration of an imaging label. Although the introduction of imaging labels on targeting vectors sounds trivial, the chemical composition of such labels has to be carefully tuned to optimize the brightness, sensitivity, and specificity of the final fluorescent tracer. To move away from traditional end-label dyes and realize the integration of fluorescence in the targeting vector itself, bifunctional fluorescent dyes have been used a.o. for biorthogonal conjugation.
As an expansion to the chemical/ biomedical efforts explored during the project, we have also extended the project activities towards the clinical arena. Here we have studied the impact that nerve sparing can have on the outcome and with that have further underlined the need for nerve sparing technologies. To help surgeons to preoperatively establish the chance of inducing nerve damage, we have clinically introduced an MRI-based preoperative nerve imaging sequence. Finally, we have teamed up with European industrial partners to create novel surgical fluorescence camera’s that support the future use of fluorescent nerve-targeting tracers.
The parallel exploration of chemical/biological and clinical/technical aspects help to strengthen the translation nature of the project and the research group. This not only has helped further strengthening of the groups position in the field of image guided surgery, it has also boosted the group’s ability to translate new (nerve imaging) technologies from molecule to man. With that another step has been made toward the further improvement of medical care in Europe.
Following the creation of a comprehensive overview of the reported tracers for peripheral nerves we have set out to develop imaging solutions for somatic and autonomic nerves that have no affinity for the central nervous system (potential site of toxicity) and have a high nerve specificity. In doing so, we have created a number of different nerve specific imaging tracers. Some target specific biomarkers in the myelin sheath or the neuronal body, while others support nerve visualization via local migration along nerves bundles. By providing these complementary nerve-imaging solutions, we have been able to cover the full biological complexity of the peripheral nerve anatomy that needs to be spared during surgery. During these efforts, we realized (local) targeting of peripheral nerves, while preventing uptake of the agents by the central nervous system. Next to the development of effective targeting vectors, a good imaging tracer relies heavily on the integration of an imaging label. Although the introduction of imaging labels on targeting vectors sounds trivial, the chemical composition of such labels has to be carefully tuned to optimize the brightness, sensitivity, and specificity of the final fluorescent tracer. To move away from traditional end-label dyes and realize the integration of fluorescence in the targeting vector itself, bifunctional fluorescent dyes have been used a.o. for biorthogonal conjugation.
As an expansion to the chemical/ biomedical efforts explored during the project, we have also extended the project activities towards the clinical arena. Here we have studied the impact that nerve sparing can have on the outcome and with that have further underlined the need for nerve sparing technologies. To help surgeons to preoperatively establish the chance of inducing nerve damage, we have clinically introduced an MRI-based preoperative nerve imaging sequence. Finally, we have teamed up with European industrial partners to create novel surgical fluorescence camera’s that support the future use of fluorescent nerve-targeting tracers.
The parallel exploration of chemical/biological and clinical/technical aspects help to strengthen the translation nature of the project and the research group. This not only has helped further strengthening of the groups position in the field of image guided surgery, it has also boosted the group’s ability to translate new (nerve imaging) technologies from molecule to man. With that another step has been made toward the further improvement of medical care in Europe.