Evaluation of Ac-Lys(0)(IRDye800CW)Tyr(3)-octreotate as a novel tracer for SSTR(2)-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 (SSTR(2)), which is overexpressed in all meningiomas. METHODS: Binding affinity of 800CW-TATE was evaluated using [(177)Lu] Lu-DOTA-Tyr(3)-octreotate displacement assays. Tumor uptake was determined by injecting 800CW-TATE in (SSTR(2)-positive) NCI-H69 or (SSTR(2)-negative) CH-157MN xenograft bearing mice and FMT2500 imaging. SSTR(2)-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. SSTR(2) 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 IC(50) 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-Tyr(3)-octreotate or administration of IRDye800CW. CH-157MN had no tumor specific tracer staining due to absence of SSTR(2) expression, thereby serving as a negative control. The tracer bound specifically to SSTR(2)-positive meningioma tissues representing all WHO grades. CONCLUSION: 800CW-TATE demonstrated sufficient binding affinity, specific SSTR(2)-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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11060-021-03739-1.