Evaluation of Ac-Lys(IRDye800CW)Tyr-octreotate as a novel tracer for SSTR-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), which is overexpressed in all meningiomas.

METHODS

Binding affinity of 800CW-TATE was evaluated using [Lu] Lu-DOTA-Tyr-octreotate displacement assays. Tumor uptake was determined by injecting 800CW-TATE in (SSTR-positive) NCI-H69 or (SSTR-negative) CH-157MN xenograft bearing mice and FMT2500 imaging. SSTR-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 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 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-octreotate or administration of IRDye800CW. CH-157MN had no tumor specific tracer staining due to absence of SSTR expression, thereby serving as a negative control. The tracer bound specifically to SSTR-positive meningioma tissues representing all WHO grades.

CONCLUSION

800CW-TATE demonstrated sufficient binding affinity, specific SSTR-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.