Preclinical Lymph Node Model for Intraoperative Molecular Imaging of Cancer.
| العنوان: | Preclinical Lymph Node Model for Intraoperative Molecular Imaging of Cancer. |
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| المؤلفون: | Bou-Samra P; University of Pennsylvania Perelman School of Medicine., Chang A; University of Pennsylvania Perelman School of Medicine., Arambepola S; University of Pennsylvania Perelman School of Medicine., Guo E; University of Pennsylvania Perelman School of Medicine., Azari F; University of Pennsylvania Perelman School of Medicine., Kennedy G; University of Pennsylvania Perelman School of Medicine., Segil A; University of Pennsylvania Perelman School of Medicine., Singhal S; University of Pennsylvania Perelman School of Medicine. |
| المصدر: | Research square [Res Sq] 2023 Jun 12. Date of Electronic Publication: 2023 Jun 12. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE |
| مستخلص: | Purpose: Lymph node(LN) dissection is part of most oncologic resections. Intraoperatively identifying a positive LN(+ LN), that harbors malignant cells, can be challenging. We hypothesized that intraoperative molecular imaging(IMI) using a cancer-targeted fluorescent prober can identify + LNs. This study aimed to develop a preclinical model of a + LN and test it using an activatable cathepsin-based enzymatic probe, VGT-309. Procedures: In the first model, we used peripheral blood mononuclear cells (PBMC), representing the lymphocytic composition of the LN, mixed with different concentrations of human lung adenocarcinoma cell line A549. Then, they were embedded in a Matrigel ® matrix. A black dye was added to mimic LN anthracosis. Model two was created using a murine spleen, the largest lymphoid organ, injected with various concentrations of A549. To test these models, we co-cultured A549 cells with VGT-309. Mean fluorescence intensity(MFI) was. An independent sample t-test was used to compare the average MFI of each A549:negative control ratio. Results: A significant difference in MFI from our PBMC control was noted when A549 cells were 25% of the LN (p = 0.046) in both 3D cell aggregate models-where the LNs native parenchyma is replaced and the one where the tumor grows over the native parenchyma. For the anthracitic equivalents of these models, the first significant MFI compared to the control was when A549 cells were 9% of the LN (p = 0.002) in the former model, and 16.7% of the LN (p = 0.033) in the latter. In our spleen model, we first noted significance in MFI when A549 cells were 16.67% of the cellular composition.(p = 0.02). Conclusions: A + LN model allows for a granular evaluation of different cellular burdens in + LN that can be assessed using IMI. This first exvivo + LN model can be used in preclinical testing of several existing dyes and in creating more sensitive cameras for IMI-guided LN detection. Competing Interests: Conflict of Interest The author(s) declare(s) that there is no conflict of interest regarding the publication of this article. |
| معلومات مُعتمدة: | P01 CA254859 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: cancer imaging; intraoperative molecular imaging; lymph node model |
| تواريخ الأحداث: | Date Created: 20230703 Latest Revision: 20231020 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC10312951 |
| DOI: | 10.21203/rs.3.rs-2953015/v1 |
| PMID: | 37398120 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.21203/rs.3.rs-2953015/v1 |
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