Paper published in ‘Journal of Neuro-oncology’

The manuscript entitled “Evaluation of Ac-Lys 0(IRDye800CW)Tyr 3-octreotate as a novel tracer for SSTR 2-targeted molecular fluorescence guided surgery in meningioma” can be found here

Abstract

Purpose Meningioma recurrence rates can be reduced by optimizing surgical resection with the use of intraoperative molecular fuorescence guided surgery (MFGS). We evaluated the potential of the fuorescent 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 afnity 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-specifc 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 afnity 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-fuorescent DOTA-Tyr3 -octreotate or administration of IRDye800CW. CH-157MN had no tumor specifc tracer staining due to absence of SSTR2 expression, thereby serving as a negative control. The tracer bound specifcally to SSTR2-positive meningioma tissues representing all WHO grades.
Conclusion 800CW-TATE demonstrated sufcient binding afnity, specifc 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.

Keywords 800CW-TATE · Intra-operative guidance · Meningioma · Molecular fuorescence guided surgery · Somatostatin receptor subtype 2

Citation

Dijkstra BM, de Jong M, Stroet MCM, Andreae F, Dulfer SE, Everts M, Kruijff S, Nonnekens J, den Dunnen WFA, Kruyt FAE, Groen RJM. Evaluation of Ac-Lys0(IRDye800CW)Tyr3-octreotate as a novel tracer for SSTR2-targeted molecular fluorescence guided surgery in meningioma. J Neurooncol. 2021 Jun;153(2):211-222. doi: 10.1007/s11060-021-03739-1. Epub 2021 Mar 26. Erratum in: J Neurooncol. 2021 May 20;: PMID: 33768405; PMCID: PMC8211583.