Article
New Somatostatin Receptor Type 2 (SSTR II)-targeted probe for near infrared fluorescence guided meningioma surgery
Nahinfrarot-Fluoreszenzgestützte Resektion von Meningeomen mittels zielgerichtetem Somatostatinrezeptor Typ 2 Fluoreszenzfarbstoff
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Authors
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Gina Fürtjes
- Universitätsklinikum Köln, Allgemeine Neurochirurgie, Köln, Deutschland; Helmholtz Zentrum München, Helmholtz Pioneer Campus, München, Deutschland
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Merle Weitzenberg
- Helmholtz Zentrum München, Institut für Medizinalchemie, Hannover, Deutschland; Helmholtz Zentrum München, Helmholtz Pioneer Campus, München, Deutschland
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Bernardo Arús
- Helmholtz Zentrum München, Helmholtz Pioneer Campus, München, Deutschland
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Hannes Rolbieski
- Helmholtz Zentrum München, Helmholtz Pioneer Campus, München, Deutschland
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Christian Mawrin
- Universitätsklinikum Magdeburg, Institut für Neuropathologie, Magdeburg, Deutschland
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Roland Goldbrunner
- Universitätsklinikum Köln, Allgemeine Neurochirurgie, Köln, Deutschland
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Oliver Plettenburg
- Helmholtz Zentrum München, Institut für Medizinalchemie, Hannover, Deutschland
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Oliver Bruns
- Helmholtz Zentrum München, Helmholtz Pioneer Campus, München, Deutschland
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Volker Neuschmelting
- Universitätsklinikum Köln, Allgemeine Neurochirurgie, Köln, Deutschland
| Published: | May 25, 2022 |
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Outline
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Objective: Meningioma mostly recur at the primary resection site demanding improvement in the intraoperative tumor visualization and surgical technique. This study aims to develop a highly specific and sensitive optical method for intraoperative meningioma imaging to guide the resection. Fluorescent dyes in the near infrared (NIR I, 700-1000nm) and shortwave infrared (SWIR, 1000-2000nm) allow detection by suitable cameras up to few millimeters in depth in real time. Our objective is to invent a fluorescent NIR I and II probe specifically targeting the somatostatin receptor type 2 (SSTR2) reliably overexpressed in meningioma independently of WHO grade and subtype.
Methods: We synthesized a SSTR2 specific probe by linking a somatostatin analogue (TATE, Tyr(3)Thr(8)-Octreotid), to a new developed dye (sNIR). Its optical properties are comparable to indocyanine green and stability as well as bleaching kinetic were tested in vitro. To evaluate pharmacokinetics and biodistribution the probe was intravenously injected in native mice and detected by a custom built camera setup focusing on physiologically overexpressing SSTR2 tissues validated by immunohistochemistry (IHC). As proof-of-principle fluorescence guided tumor resection was performed in an ectopic and orthotopic meningioma IOMM-Lee mouse model.
Results: The SSTR2-sNIR probe is stable in aqueous solution up to 12h with favorable optical properties regarding kinetics, biodistribution and photostability compared to its IRDye800 analogue. In vivo, we observed a highly specific physiological signal uptake in the gastric epithelium and pancreas (both are highly expressing SSTR2 on IHC) compared to autofluorescence and negative controls. Given the moderate SSTR2 expression in the preclinical meningioma model we could still detect a mean tumor-to-normal-tissue ratio of 1.97 (n = 3; SD 0.63) in the ectopic and of 4.75 (n = 5; SD 1.33) in the orthotopic meningioma mouse model, respectively, allowing the fluorescence guidance to be feasible.
Conclusion: Our preclinical results demonstrate that the newly developed SSTR2-targeted fluorescent probe is stable in various biological media over time and capable of specifically targeting the SSTR2 in vitro and in vivo potentially enabling sensitive and specific meningioma fluorescent guided surgery in the future. Figure 1 [Fig. 1]
