Evaluation of Ac-Lys⁰(IRDye800CW)Tyr³-octreotate as a novel tracer for SSTR₂-targeted molecular fluorescence guided surgery in meningioma

Purpose: Meningioma recurrence rates can be reduced by optimizing surgical resection with the use of intraoperative molecular fluorescence guided surgery (MFGS). We evaluated the potential of the fluorescent tracer 800CW-TATE for MFGS using in vitro and in vivo models. It targets somatostatin receptor subtype 2 (SSTR₂), which is overexpressed in all meningiomas. Methods: Binding affinity of 800CW-TATE was evaluated using [¹⁷⁷Lu] Lu-DOTA-Tyr³-octreotate displacement assays. Tumor uptake was determined by injecting 800CW-TATE in (SSTR₂-positive) NCI-H69 or (SSTR₂-negative) CH-157MN xenograft bearing mice and FMT2500 imaging. SSTR₂-specific binding was measured by comparing tumor uptake in NCI-H69 and CH-157MN xenografts, blocking experiments and non-targeted IRDye800CW-carboxylate binding. Tracer distribution was analyzed ex vivo, and the tumor-to-background ratio (TBR) was calculated. SSTR₂ expression was determined by immunohistochemistry (IHC). Lastly, 800CW-TATE was incubated on frozen and fresh meningioma specimens and analyzed by microscopy. Results: 800CW-TATE binding affinity assays showed an IC₅₀ value of 72 nM. NCI-H69 xenografted mice showed a TBR of 21.1. 800CW-TATE detection was reduced after co-administration of non-fluorescent DOTA-Tyr³-octreotate or administration of IRDye800CW. CH-157MN had no tumor specific tracer staining due to absence of SSTR₂ expression, thereby serving as a negative control. The tracer bound specifically to SSTR₂-positive meningioma tissues representing all WHO grades. Conclusion: 800CW-TATE demonstrated sufficient binding affinity, specific SSTR₂-mediated tumor uptake, a favorable biodistribution, and high TBR. These features make this tracer very promising for use in MFGS and could potentially aid in safer and a more complete meningioma resection, especially in high-grade meningiomas or those at complex anatomical localizations.