Search

Although introduced decades ago, few cyanoacrylate glues have been approved for endovascular use, despite evidence of their usefulness, notably for complex procedures suchas hemostatic embolization. Indications include massive bleeding requiring emergent hemostasis and prevention of severe bleeding during scheduled surgery to remove a hypervascular tumor. Adding radiopaque Lipiodol Ultra Fluid® (LUF) modulates glue polymerization and allows fluoroscopic guidance, but few comparative in vivo studies have assessed the impact of the resulting change in glue concentration or of other factors such as target-vessel blood flow. In a rabbit model, we used ex vivo X-ray microtomography to assess the results of in vivo renal-artery embolization by various mixtures of N-butyl cyanoacrylate (NBCA), metacryloxysulfolane, and LUF. Overall, penetration to the superficial interlobular arteries was achieved in about two-thirds of cases and into the capillaries in nearly half the cases, while cast fragmentation was seen in slightly more than half the cases. Greater NBCA dilution and the blocked-blood-flow technique were independently associated with greater distality of penetration. Blocked-blood-flow injection was independently associated with absence of fragmentation, capillary penetration, a shorter cast-to-capsule distance, and higher cast attenuation. A larger mixture volume was independently associated with higher indexed cast ratio and deeper penetration. Finally, microtomography is an adapted tool to assess ex vivo distribution of glue cast. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancers and is not eligible for hormone and anti-HER2 therapies. Identifying therapeutic targets and associated biomarkers in TNBC is a clinical challenge to improve patients' outcome and management. High infiltration of CD206+ M2-like macrophages in the tumor microenvironment (TME) indicates poor prognosis and survival in TNBC patients. As we previously showed that membrane expression of GRP94, an endoplasmic reticulum chaperone, was associated with the anti-inflammatory profile of human PBMC-derived M2 macrophages, we hypothesized that intra-tumoral CD206+ M2 macrophages expressing GRP94 may represent innovative targets in TNBC for theranostic purposes. We demonstrate in a preclinical model of 4T1 breast tumor-bearing BALB/c mice that (i) CD206-expressing M2-like macrophages in the TME of TNBC can be specifically detected and quantified using in vivo SPECT imaging with 99mTc-Tilmanocept, and (ii) the inhibition of GRP94 with the chemical inhibitor PU-WS13 induces a decrease in CD206-expressing M2-like macrophages in TME. This result correlated with reduced tumor growth and collagen content, as well as an increase in CD8+ cells in the TME. 99mTc-Tilmanocept SPECT imaging might represent an innovative non-invasive strategy to quantify CD206+ tumor-associated macrophages as a biomarker of anti-GRP94 therapy efficacy and TNBC tumor aggressiveness. [ABSTRACT FROM AUTHOR]