Magnetic resonance molecular imaging for non-invasive precision cancer diagnosis

Lü, Zheng Rong

doi:10.1016/j.cobme.2017.11.003

Cited by 11 publications

(7 citation statements)

References 31 publications

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“…Compared with other molecular imaging modalities, low sensitivity for molecular detection is the major shortcoming. 67 Optical imaging mainly includes bioluminescence imaging (BLI) and fluorescence imaging (FLI). The relatively low implementation, high sensitivity, and nonradioactive properties make this noninvasive imaging technique preferred in preclinical research.…”

Section: Overview On Molecular Imagingmentioning

confidence: 99%

Molecular imaging of tumor-associated macrophages in cancer immunotherapy

Wang

Zhang

et al. 2022

Ther Adv Med Oncol

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Tumor-associated macrophages (TAMs), the most abundant inflammatory cell group in the tumor microenvironment, play an essential role in tumor immune regulation. The infiltration degree of TAMs in the tumor microenvironment is closely related to tumor growth and metastasis, and TAMs have become a promising target in tumor immunotherapy. Molecular imaging is a new interdisciplinary subject that combines medical imaging technology with molecular biology, nuclear medicine, radiation medicine, and computer science. The latest progress in molecular imaging allows the biological processes of cells to be visualized in vivo, which makes it possible to better understand the density and distribution of macrophages in the tumor microenvironment. This review mainly discusses the application of targeting TAM in tumor immunotherapy and the imaging characteristics and progress of targeting TAM molecular probes using various imaging techniques.

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Section: Overview On Molecular Imagingmentioning

confidence: 99%

Molecular imaging of tumor-associated macrophages in cancer immunotherapy

Wang

Zhang

et al. 2022

Ther Adv Med Oncol

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“…However, MR molecular imaging (MRMI) for non-invasive assessment and treatment monitoring of drug-resistant CRC has never been performed before. To address this challenge, to circumvent the immune and translational hurdles of MNPs, and to potentially target a broader range of drug-resistant cancers, we developed MRMI strategies to target the abundantly expressed oncoprotein extradomain-B fibronectin (EDB-FN) in the tumor extracellular matrix (ECM) 33 - 35 .…”

Section: Introductionmentioning

confidence: 99%

Noninvasive assessment and therapeutic monitoring of drug-resistant colorectal cancer by MR molecular imaging of extradomain-B fibronectin

Vaidya¹,

Ayat²,

Buford³

et al. 2020

Theranostics

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Antineoplastic resistance represents a multifaceted challenge for cancer therapy and diagnostics. Extensive molecular heterogeneity, even within neoplasms of the same type, can elicit distinct outcomes of administering therapeutic pressures, frequently leading to the development of drug-resistant populations. Improved success of oncotherapies merits the exploration of precise molecular imaging technologies that can detect not only anatomical but also molecular changes in tumors and their microenvironment, early on in the treatment regimen. To this end, we developed magnetic resonance molecular imaging (MRMI) strategies to target the extracellular matrix oncoprotein, extradomain-B fibronectin (EDB-FN), for non-invasive assessment and therapeutic monitoring of drug-resistant colorectal cancer (CRC). Methods: Two drug-resistant CRC lines generated from parent DLD-1 and RKO cells by long-term treatment with 5ʹ-FU and 5ʹ-FU plus CB-839 respectively, were characterized for functional and gene expression changes using 3D culture, transwell invasion, qRT-PCR, and western blot assays. Contrast-enhanced MRMI of EDB-FN was performed in athymic nu/nu mice bearing subcutaneous tumor xenografts with 40 µmol/kg dose of macrocyclic ZD2-targeted contrast agent MT218 [ZD2-N 3 -Gd (HP-DO3A)] on a 3T MRS 3000 scanner. Immunohistochemistry was conducted on patient specimens and xenografts using anti-EDB-FN antibody G4. Results: Analyses of TCGA and GTEx databases revealed poor prognosis of colon cancer patients with higher levels of EDB-FN. Similarly, immunohistochemical staining of patient specimens showed increased EDB-FN expression in primary colon adenocarcinoma and hepatic metastases, but none in normal adjacent tissues. Drug-resistant DLD1-DR and RKO-DR cells were also found to demonstrate enhanced invasive potential and significantly elevated EDB-FN expression over their parent counterparts. MRMI of EDB-FN with 40 µmol/kg dose of MT218 (60% lower than the clinical dose) resulted in robust signal enhancement in the drug-resistant CRC xenografts with 84-120% increase in their contrast-to-noise ratios (CNRs) over the non-resistant counterparts. The feasibility of non-invasive therapeutic monitoring using MRMI of EDB-FN was also evaluated in drug-resistant DLD1-DR tumors treated with a pan-AKT inhibitor MK2206-HCl. The treated drug-resistant tumors failed to respond to therapy, which was accurately detected by MRMI with MT218, demonstrating higher signal enhancement and increased CNRs in the 4-week follow-up scans over the pre-treatment scans. Conclusions: EDB-FN is a promising molecular marker for assessing drug resistance. MRMI of EDB-FN with MT218 at a significantly reduced dose can facilitate effective non-invasive assessment and treatment response monitoring of drug-resistant CRC, highlighting its translational potential for active surveillance and management of CRC and other malignancies.

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“…The drug delivery concept can be applied to increase the concentration of diagnostic agents in microscopic tumors to improve the sensitivity of clinical diagnostic modalities for accurate early cancer detection and diagnosis. We have developed novel clinically translatable targeted MRI contrast agents using the concept of targeted drug delivery to improve the sensitivity of magnetic resonance molecular imaging (MRMI) for early detection and risk stratification of aggressive malignancies. ,, The conjugation of peptides specific to abundant extracellular matrix proteins associated with tumor aggressiveness facilitates the delivery of a sufficient amount of the contrast agents to generate detectable signals for high sensitivity detection of microscopic tumors and risk stratification in both prostate and breast cancer in animal models. ,, A liposomal system carrying near-infrared dyes has shown great promise in identifying metastatic lesions of breast cancer with optical imaging . Early detection and risk stratification of aggressive tumors will provide an opportunity for early intervention at a treatable stage for curative outcomes with existing therapeutic approaches. − It may be less challenging for targeted drug delivery into cancer cells in microscopic tumors via systemic approaches as compared to advanced tumors.…”

Section: Future Perspectives Of Drug Delivery In Cancer Therapymentioning

confidence: 99%

Drug Delivery in Cancer Therapy, Quo Vadis?

Lü

Qiao

2018

Mol. Pharmaceutics

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The treatment of malignancies has undergone dramatic changes in the past few decades. Advances in drug delivery techniques and nanotechnology have allowed for new formulations of old drugs, so as to improve the pharmacokinetics, to enhance accumulation in solid tumors, and to reduce the significant toxic effects of these important therapeutic agents. Here, we review the published clinical data in cancer therapy of several major drug delivery systems, including targeted radionuclide therapy, antibody-drug conjugates, liposomes, polymer-drug conjugates, polymer implants, micelles, and nanoparticles. The clinical outcomes of these delivery systems from various phases of clinical trials are summarized. The success and limitations of the drug delivery strategies are discussed based on the clinical observations. In addition, the challenges in applying drug delivery for efficacious cancer therapy, including physical barriers, tumor heterogeneity, drug resistance, and metastasis, are discussed along with future perspectives of drug delivery in cancer therapy. In doing so, we intend to underscore that efficient delivery of cancer therapeutics to solid malignancies remains a major challenge in cancer therapy, and requires a multidisciplinary approach that integrates knowledge from the diverse fields of chemistry, biology, engineering, and medicine. The overall objective of this review is to improve our understanding of the clinical fate of commonly investigated drug delivery strategies, and to identify the limitations that must be addressed in future drug delivery strategies, toward the pursuit of curative therapies for cancer.

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Magnetic resonance molecular imaging for non-invasive precision cancer diagnosis

Cited by 11 publications

References 31 publications

Molecular imaging of tumor-associated macrophages in cancer immunotherapy

Molecular imaging of tumor-associated macrophages in cancer immunotherapy

Noninvasive assessment and therapeutic monitoring of drug-resistant colorectal cancer by MR molecular imaging of extradomain-B fibronectin

Drug Delivery in Cancer Therapy, Quo Vadis?

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