Evaluation of Ac-Lys(0)(IRDye800CW)Tyr(3)-octreotate as a novel tracer for SSTR2-targeted molecular fluorescence guided surgery in meningioma

Bianca M Dijkstra, Marion de Jong, Marcus C M Stroet, Fritz Andreae, Sebastiaan E Dulfer, Marieke Everts, Schelto Kruijff, Julie Nonnekens, Wilfred F A den Dunnen, Frank A E Kruyt, Rob J M Groen*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

8 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Aantal pagina's12
TijdschriftJOURNAL OF NEURO-ONCOLOGY
DOI's
StatusE-pub ahead of print - 26-mrt-2021

Citeer dit