NIMG-75. ANALYZING THE INTERFACE BETWEEN MRI AND DRUG DISTRIBUTION USING ORTHOTOPIC GBM-DERIVED XENOGRAFT (PDX) MODELS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi146-vi146
Author(s):  
Sameer Channar ◽  
Sara Ranjbar ◽  
Pamela Jackson ◽  
Leland Hu ◽  
Michael Regan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cell Lines ◽  
Mean Squared Error ◽  
Drug Distribution ◽  
Normal Brain ◽  
Imaging Features ◽  
Visible Image ◽  
Drug Levels ◽  
Mri Features ◽  
Pdx Models

Abstract INTRODUCTION Glioblastoma (GBM) is a diffusely invasive primary brain tumor with significant spread of tumor cells to the periphery of visible image abnormality. Enhancement of Gadolinium (Gd) contrast agent on magnetic resonance imaging (MRI) has historically been considered a confirmation of local breakdown of the blood brain barrier (BBB) and sufficient drug delivery to the bulk of tumors. In this work, we used GBM-derived xenograft (PDX) models to compare drug delivery in GBM brain for high and low BBB-permeable drugs. MATERIALS AND METHODS Five patient-derived orthotopic xenograft models from two GBM cell lines (GBM39 and GBM12) were co-dosed with erlotinib and osimertinib, two drugs with low and high BBB-permeability, respectively. T1Gd and T2-weighted MRIs were acquired from all animals prior to model sacrifice. Tumors were manually segmented on denoised and standardized MRIs and intensity patterns were captured using first and second order statistical features in the moving 3x3 kernel. We compared drug levels found in Matrix Assisted Laser Desorption Ionization (MALDI) in T1Gd enhancement, T2 enhancement, and normal brain. We also performed linear regression modeling to predict drug levels using MRI features. Model performance was measured using root mean squared error (RMSE). RESULTS Our analysis showed correlations between imaging features and MALDI drug levels. Osimertinib had a uniform distribution across the brain for all animals and all cell lines, consistent with our expectation for a high BBB-penetrant drug. Erlotinib showed the highest drug levels in T2 for GBM39 and in T1Gd for GBM12. Regression models showed promising results for predicting Erlotinib with a low RMSE of 0.037. CONCLUSION Our preliminary results suggest MRI can be predictive of drug levels for low-BBB penetrant drugs. Understanding the relationship between MRIs and drug distribution in diffuse tumors can be beneficial to developing effective treatment.

scholarly journals Treatment of Recurrent Glioblastoma by Chronic Convection-Enhanced Delivery of Topotecan

2021 ◽  
Author(s):  
Eleonora F. Spinazzi ◽  
Michael G. Argenziano ◽  
Pavan S. Upadhyayula ◽  
Matei A. Banu ◽  
Justin A. Neira ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Distribution ◽  
Response Assessment ◽  
Recurrent Glioblastoma ◽  
Normal Brain ◽  
Convection Enhanced Delivery ◽  
Before And After ◽  
Treatment Response Assessment ◽  
Slow Cycling ◽  
Novel Drug

ABSTRACTGlioblastoma, the most common primary brain malignancy, is invariably fatal. Systemic chemotherapy is ineffective mostly because of drug delivery limitations. To overcome this, we devised an internalized pump-catheter system for direct chronic convection-enhanced delivery (CED) into peritumoral brain tissue. Topotecan (TPT) by chronic CED in 5 patients with refractory glioblastoma selectively eliminated tumor cells without toxicity to normal brain. Large, stable drug distribution volumes were non-invasively monitored with MRI of co-infused gadolinium. Analysis of multiple radiographically localized biopsies taken before and after treatment showed a decreased proliferative tumor signature resulting in a shift to a slow-cycling mesenchymal/astrocytic-like population. Tumor microenvironment analysis showed an inflammatory response and preservation of neurons. This novel drug delivery strategy and innovative clinical trial paradigm overcomes current limitations in delivery and treatment response assessment as shown here for glioblastoma and is potentially applicable for other anti-glioma agents as well as other CNS diseases.

Myxofibrosarcoma: clinical and prognostic value of MRI features

2020 ◽  
Vol 16 ◽  
Author(s):  
Paolo Spinnato ◽  
Andrea Sambri ◽  
Tomohiro Fujiwara ◽  
Luca Ceccarelli ◽  
Roberta Clinca ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Local Recurrence ◽  
Contrast Enhancement ◽  
Imaging Modality ◽  
Soft Tissue Sarcomas ◽  
The Elderly ◽  
High Rate ◽  
Imaging Features ◽  
High Grade ◽  
Mri Features

: Myxofibrosarcoma is one of the most common soft tissue sarcomas in the elderly. It is characterized by an extremely high rate of local recurrence, higher than other soft tissue tumors, and a relatively low risk of distant metastases.Magnetic resonance imaging (MRI) is the imaging modality of choice for the assessment of myxofibrosarcoma and plays a key role in the preoperative setting of these patients.MRI features associated with high risk of local recurrence are: high myxoid matrix content (water-like appearance of the lesions), high grade of contrast enhancement, presence of an infiltrative pattern (“tail sign”). On the other hand, MRI features associated with worse sarcoma specific survival are: large size of the lesion, deep location, high grade of contrast enhancement. Recognizing the above-mentioned imaging features of myxofibrosarcoma may be helpful to stratify the risk for local recurrence and disease-specific survival. Moreover, the surgical planning should be adjusted according to the MRI features

scholarly journals LPTO-06. A NOVEL BRAIN-PERMEANT CHEMOTHERAPEUTIC AGENT FOR THE TREATMENT OF BREAST CANCER LEPTOMENINGEAL METASTASIS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i7-i7
Author(s):  
Jiaojiao Deng ◽  
Sophia Chernikova ◽  
Wolf-Nicolas Fischer ◽  
Kerry Koller ◽  
Bernd Jandeleit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Tumors ◽  
Cell Lines ◽  
Chemotherapeutic Agent ◽  
Leptomeningeal Metastasis ◽  
Breast Cancer Cell Lines ◽  
Normal Brain ◽  
Breast Cancers

Abstract Leptomeningeal metastasis (LM), a spread of cancer to the cerebrospinal fluid and meninges, is universally and rapidly fatal due to poor detection and no effective treatment. Breast cancers account for a majority of LMs from solid tumors, with triple-negative breast cancers (TNBCs) having the highest propensity to metastasize to LM. The treatment of LM is challenged by poor drug penetration into CNS and high neurotoxicity. Therefore, there is an urgent need for new modalities and targeted therapies able to overcome the limitations of current treatment options. Quadriga has discovered a novel, brain-permeant chemotherapeutic agent that is currently in development as a potential treatment for glioblastoma (GBM). The compound is active in suppressing the growth of GBM tumor cell lines implanted into the brain. Radiolabel distribution studies have shown significant tumor accumulation in intracranial brain tumors while sparing the adjacent normal brain tissue. Recently, we have demonstrated dose-dependent in vitro and in vivo anti-tumor activity with various breast cancer cell lines including the human TNBC cell line MDA-MB-231. To evaluate the in vivo antitumor activity of the compound on LM, we used the mouse model of LM based on the internal carotid injection of luciferase-expressing MDA-MB-231-BR3 cells. Once the bioluminescence signal intensity from the metastatic spread reached (0.2 - 0.5) x 106 photons/sec, mice were dosed i.p. twice a week with either 4 or 8 mg/kg for nine weeks. Tumor growth was monitored by bioluminescence. The compound was well tolerated and caused a significant delay in metastatic growth resulting in significant extension of survival. Tumors regressed completely in ~ 28 % of treated animals. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, Quadriga’s new agent could be effective as a therapeutic for both primary and metastatic brain tumors such as LM. REF: https://onlinelibrary.wiley.com/doi/full/10.1002/pro6.43

scholarly journals Head and neck osteosarcoma: CT and MR imaging features

2020 ◽  
Vol 49 (2) ◽  
pp. 20190202
Author(s):  
Zhendong Luo ◽  
Weiguo Chen ◽  
Xinping Shen ◽  
Genggeng Qin ◽  
Jianxiang Yuan ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Head And Neck ◽  
Giant Cell ◽  
High Signal ◽  
Imaging Features ◽  
Matrix Mineralization ◽  
Imaging Characteristics ◽  
Mri Features ◽  
Signal Intensities ◽  
Ct And Mri

Objective: This study aims to assess the CT and MRI features of head and neck osteosarcoma (HNO). Methods: 37 HNOs were identified, and the following imaging characteristics were reviewed on CT and MRI. Results: A total of 37 patients(age 41.5 ± 15.0 years old; 16 males, 21 females) were included in the study. Tumours occurred in the maxilla (16, 43.2%), mandible (8, 21.6%), skull base (6, 16.2%), calvarium (5, 13.5%), paranasal sinuses (1, 2.7%) and cervical soft tissue (1, 2.7%). 16 patients received radiotherapy for nasopharyngeal carcinoma. Three patients (8.1%) developed osteosarcomas related to a primary bone disease. 16 of the (43.2%) tumours demonstrated lytic density on CT scans, followed by 13 (35.1%) showing mixed density and 7 (18.9%) with sclerotic density. Matrix mineralization was present in 32 (86.5%). 3 out of 24 (12.5%) tumours showed lamellar periosteal reactions, 21 out of 24 (87.5%) showed spiculated periosteal reactions. 12 tumours showed low signal intensities on T1WI, with 16 having heterogeneous signal intensities. 10 tumours showed high signal intensities on T2WI, and 18 showed heterogeneous signal intensities. With contrast-enhanced images, 3 tumours showed homogeneous enhancement (2 osteoblastic and 1 giant cell-rich), 18 tumours showed heterogeneous enhancement (13 osteoblastic, 4 fibroblastic and 1 giant cell-rich), and 7 tumours showed peripheral enhancement (6 chondroblastic and 1 osteoblastic). These tumours were characterized by soft tissue masses with a diameter of 5.6 ± 1.8 cm. Conclusions: HNO is a rare condition and is commonly associated with previous radiation exposure. This study provides age, sex distribution, location, CT and MRI features of HNO.

scholarly journals Synthesis and Characterization of Chitosan-Based Nanodelivery Systems to Enhance the Anticancer Effect of Sorafenib Drug in Hepatocellular Carcinoma and Colorectal Adenocarcinoma Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 497
Author(s):  
Umme Ruman ◽  
Kalaivani Buskaran ◽  
Giorgia Pastorin ◽  
Mas Jaffri Masarudin ◽  
Sharida Fakurazi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Delivery ◽  
Cell Lines ◽  
Delivery System ◽  
Colorectal Adenocarcinoma ◽  
Dermal Fibroblast ◽  
Spherical Shape ◽  
Ht29 Cell ◽  
Normal Human Dermal Fibroblast ◽  
Cancer Management

The formation of two nanodelivery systems, Sorafenib (SF)-loaded chitosan (SF-CS) and their folate-coated (SF-CS-FA) nanoparticles (NPs), were developed to enhance SF drug delivery on human Hepatocellular Carcinoma (HepG2) and Colorectal Adenocarcinoma (HT29) cell lines. The ionic gelation method was adopted to synthesize the NPs. The characterizations were performed by DLS, FESEM, TEM, XRD, TGA, FTIR, and UV-visible spectroscopy. It was found that 83.7 ± 2.4% and 87.9 ± 1.1% of encapsulation efficiency; 18.2 ± 1.3% and 19.9 ± 1.4% of loading content; 76.3 ± 13.7 nm and 81.6 ± 12.9 nm of hydrodynamic size; 60–80 nm and 70–100 nm of TEM; and FESEM sizes of near-spherical shape were observed, respectively, for SF-CS and SF-CS-FA nanoparticles. The SF showed excellent release from the nanoparticles under pH 4.8 PBS solution, indicating a good delivery system for tumor cells. The cytotoxicity study revealed their better anticancer action towards HepG2 and HT29 cell lines compared to the free sorafenib. Moreover, both NPs systems showed negligible toxicity to normal Human Dermal Fibroblast adult cells (HDFa). This is towards an enhanced anticancer drug delivery system with sustained-release properties for better cancer management.

scholarly journals CTNI-03. IMAGING FEATURES OF LEPTOMENINGEAL METASTASES OF NON-SMALL CELL LUNG CANCER: A SINGLE-CENTER REAL-WORLD STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii41-ii41
Author(s):  
Junjie Zhen ◽  
Lei Wen ◽  
Shaoqun Li ◽  
Mingyao Lai ◽  
Changguo Shan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Type A ◽  
Brain Parenchyma ◽  
Imaging Features ◽  
Type B ◽  
Type D ◽  
Mri Examination ◽  
Mri Features ◽  
Brain And Spinal Cord ◽  
The Brain

Abstract BACKGROUND According to EANO-ESMO clinical practice guidelines, the MRI findings of LM are divided into 4 types, namely linear enhancement (type A), nodular enhancement (type B), linear combined with nodular enhancement (type C), and sign of hydrocephalus (type D). METHODS The MRI features of brain and spinal cord in patients diagnosed with NSCLC-LM in Guangdong Sanjiu Brain Hospital from 2010 until 2019 were investigated, and then were classified into 4 types. The imaging features were analyzed. RESULTS A total of 80 patients were enrolled in the study. The median age of the patients was 53.5 years old, and the median time from the initial diagnosis to the confirmed diagnosis of LM was 11.6 months. The results of enhanced MRI examination of the brain in 79 cases showed that the number of cases with enhancements of type A, B, C and D were 50 (63.3%), 0, 26 (32.9%) and 3 (3.8%), respectively, and that LM with metastases to the brain parenchyma was found in 42 cases (53.2%). The results of enhanced MRI examination of spinal cord in 59 cases showed that there were only enhancements of type A and C in 40 cases (67.8%) and 3 cases (5.0%), and no enhancement sign in the other 16 cases (27.2%). CONCLUSION MRI examination of brain and spinal cord will improve the detection rate of LM. The MRI features of NSCLC-LM in real world are mainly characterized by the linear enhancements of brain and spinal cord, followed by linear combined with nodular enhancement. The enhancements of type B and type D are rare in clinic. Almost half of the patients have LM and metastases to the brain parenchyma. Therefore, the differentiation of tumor metastases is needed to be paid attention to for the early diagnosis and the formulation of reasonable treatment plans.

Transcription factor 3 controls cell proliferation and migration in glioblastoma multiforme cell lines

2016 ◽  
Vol 94 (3) ◽  
pp. 247-255 ◽  
Author(s):  
Ruiting Li ◽  
Yinghui Li ◽  
Xin Hu ◽  
Haiwei Lian ◽  
Lei Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glioblastoma Multiforme ◽  
Cell Lines ◽  
Normal Brain ◽  
Phosphatidylinositol 3 Kinase ◽  
T Cell Factor ◽  
And Migration ◽  
Induced Apoptosis ◽  
Proliferation And Migration ◽  
Transcription Factor 3

Transcription factor 3 (TCF3) is a member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family. Recent studies have demonstrated its potential carcinogenic properties. Here we show that TCF3 was upregulated in glioma tissues compared with normal brain tissues. This upregulation of the TCF3 gene probably has functional significance in brain-tumor progression. Our studies on glioblastoma multiforme (GBM) cell lines show that knock-down of TCF3 induced apoptosis and inhibited cell migration. Further analysis revealed that down-regulation of TCF3 gene expression inhibits Akt and Erk1/2 activation, suggesting that the carcinogenic properties of TCF3 in GBM are partially mediated by the phosphatidylinositol 3-kinase–Akt and MAPK–Erk signaling pathways. Considered together, the results of this study demonstrate that high levels of TCF3 in gliomas potentially promote glioma development through the Akt and Erk pathways.

scholarly journals Multimodal imaging patterns predict survival in recurrent glioblastoma patients treated with bevacizumab

2016 ◽  
Vol 18 (12) ◽  
pp. 1680-1687 ◽  
Author(s):  
Ken Chang ◽  
Biqi Zhang ◽  
Xiaotao Guo ◽  
Min Zong ◽  
Rifaquat Rahman ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Progression Free Survival ◽  
Clinical Decision ◽  
Recurrent Glioblastoma ◽  
Machine Learning Techniques ◽  
Imaging Biomarkers ◽  
Imaging Features ◽  
Mri Features ◽  
Fluid Attenuated Inversion Recovery ◽  
Multimodal Mri

Abstract Background Bevacizumab is a humanized antibody against vascular endothelial growth factor approved for treatment of recurrent glioblastoma. There is a need to discover imaging biomarkers that can aid in the selection of patients who will likely derive the most survival benefit from bevacizumab. Methods The aim of the study was to examine if pre- and posttherapy multimodal MRI features could predict progression-free survival and overall survival (OS) for patients with recurrent glioblastoma treated with bevacizumab. The patient population included 84 patients in a training cohort and 42 patients in a testing cohort, separated based on pretherapy imaging date. Tumor volumes of interest were segmented from contrast-enhanced T1-weighted and fluid attenuated inversion recovery images and were used to derive volumetric, shape, texture, parametric, and histogram features. A total of 2293 pretherapy and 9811 posttherapy features were used to generate the model. Results Using standard radiographic assessment criteria, the hazard ratio for predicting OS was 3.38 (P < .001). The hazard ratios for pre- and posttherapy features predicting OS were 5.10 (P < .001) and 3.64 (P < .005) for the training and testing cohorts, respectively. Conclusion With the use of machine learning techniques to analyze imaging features derived from pre- and posttherapy multimodal MRI, we were able to develop a predictive model for patient OS that could potentially assist clinical decision making.

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