In:
Journal of Neuro-Oncology, Springer Science and Business Media LLC, Vol. 153, No. 2 ( 2021-06), p. 211-222
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0167-594X
,
1573-7373
DOI:
10.1007/s11060-021-03739-1
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2007293-4
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