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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211583 | PMC |
http://dx.doi.org/10.1007/s11060-021-03739-1 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!