EU Society of Molecular Imaging Meeting ..Aug 25 2021..Poster from France...Tilmanocept Potential To | NAVB Message Board Posts


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Msg  34684 of 34981  at  7/31/2021 10:46:27 AM  by

moneyonomics

The following message was updated on 7/31/2021 10:49:29 AM.

EU Society of Molecular Imaging Meeting ..Aug 25 2021..Poster from France...Tilmanocept Potential To Quantify CD206 in TAMS

 
"...99mTc-Tilmanocept SPECT imaging might represent an innovative non-invasive strategy to quantify CD206+ tumor- associated macrophages as a biomarker relevant for prognosis, therapeutic prediction and/or monitoring of solid tumors. The potential effects of PU-WS13 on the modulation of M2-like macrophages are currently investigated..."


121--99mTc-Timanocept Spect Imaging As A Potential Non-Invasive Method To Quantify CD206+ Tumor-Associated M2-like Macrophages

Alexanne Bouchard1, 3, Hugo Sikner1, 3, Mathieu Moreau2, Emeric Limagne3, Pierre-Simon Bellaye3, 1, Evelyne Kohli1, Bertrand Collin2, 3

1 Université de Bourgogne Franche comté, UMR / INSERM / Ub / Agrosup / 1231, Dijon, France
2 Université de Bourgogne Franche Comté, UMR / Ub / CNRS / 6302, Dijon, France
3 Centre anticancéreux Georges François Leclerc, Dijon, France

Introduction

In oncology, modulation of tumor microenvironment (TME) and its follow-up by molecular imaging is crucial because of its central role in cancer. In the TME, M2-like macrophages have been associated with cancer aggressiveness, therapy resistance and poor prognosis. The aim of our study was to assess if M2-like macrophages (i) could be tracked in vivo into the TME with SPECT imaging and (ii) could be modulated by the inhibition of Gp96, an ER chaperone involved in inflammatory processes that we have previously shown to be expressed at the cell membrane of human M2 macrophages [1].

Methods

Tissues from mouse triple negative breast cancer (TNBC, 4T1 cell line) and colon cancer (CC, CT26 cell line) were analyzed by immunohistochemistry (IHC) to detect the presence of Gp96 and CD206 (a marker of M2 macrophages) into the TME. Specific CD206 in vivo imaging on 4T1- and CT26-tumor bearing mice receiving or not a specific inhibitor of Gp96 (PU-WS13) was performed with 99mTc-Tilmanocept SPECT (i.v injection, 15MBq/mouse). Images were performed at 1h, 4h and 24h post-injection. Ex vivo gamma counting of tumors was performed after the last imaging. Radioactivity content measured with gamma counting or on images was expressed as percentage of the injected dose per gram of tissue (% ID/g). For 4T1 tumors, tumor growth and collagen content were also assessed.

Results/Discussion

IHC experiments demonstrated an overexpression of Gp96 in tumor cells as well as the presence of M2-like macrophages expressing both CD206 and Gp96 in 4T1 tumors while CT26 tumors only showed an upregulation of Gp96. These results are confirmed with in vivo SPECT imaging. 99mTc-Tilmanocept tumor uptake was significantly higher in 4T1- compared to CT26-tumor bearing mice (2.53 %ID/g and 1.08 %ID/g respectively, p=0.009). Based on these results, the 4T1 model was chosen to study the impact of Gp96 inhibition. Interestingly, PU-WS13 induced a significant decrease in 99mTc-Tilmanocept tumor uptake compared to untreated mice (1.12 %ID/g and 0.78 %ID/g respectively, p=0.0011) as well as a lower number of CD206+ M2-like macrophages compared to untreated mice. These results correlated with a reduced tumor growth and collagen content in 4T1 tumors.

Conclusions

99mTc-Tilmanocept SPECT imaging might represent an innovative non-invasive strategy to quantify CD206+ tumor- associated macrophages as a biomarker relevant for prognosis, therapeutic prediction and/or monitoring of solid tumors. The potential effects of PU-WS13 on the modulation of M2-like macrophages are currently investigated.

Disclosure

I or one of my co-authors have no financial interest or relationship to disclose regarding the subject matter of the presentation
 
 


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