Imaging In Cancer Research Research Articles

Optical molecular imaging in cancer research: current impact and future prospect

Abstract Cancer has long been a major threat to human health. Recent advancements in molecular imaging have revolutionized cancer research by enabling early and precise disease localization, essential for effective management. In particular, optical molecular imaging is an invaluable cancer detection tool in preoperative planning, intraoperative guidance, and postoperative monitoring owing to its noninvasive nature, rapid turnover, safety, and ease of use. The tumor microenvironment and cells within it express distinct biomarkers. Optical imaging technology leverages these markers to differentiate tumor tissues from surrounding tissues and capture real-time images with high resolution. Nevertheless, a robust understanding of these cancer-related molecules and their dynamic changes is crucial for effectively managing cancer. Recent advancements in optical molecular imaging technologies offer novel approaches for cancer investigation in research and practice. This review investigates the modern optical molecular imaging techniques employed in both preclinical and clinical research, including bioluminescence, fluorescence, chemiluminescence, photoacoustic imaging, and Raman spectroscopy. We explore the current paradigm of optical molecular imaging modalities, their current status in preclinical cancer research and clinical applications, and future perspectives in the fields of cancer research and treatment.

Rapid Construction of 18F-Triazolyl-tetrazines through the Click Reaction.

Due to the fast reaction rate, 18F-labeled tetrazines have been widely applied in positron emission tomography (PET) imaging in cancer research and drug discovery. In this work, several functional 18F-triazolyl-tetrazines were rapidly obtained through an optimized copper-catalyzed alkyene-azide cycloaddition reaction system in >99% radiochemical conversions. Notably, the commonly used 18F-labeled azides were isolated through cartridges and directly used for cycloadditions, which greatly simplified the labeling procedure. The assembled triazolyl-tetrazines demonstrated high in vitro stability and reaction kinetics, exhibiting considerable potential for the development of PET agents.

Recent Advances and Applications of Ambient Mass Spectrometry Imaging in Cancer Research: An Overview.

Cancer metabolic variability has a significant impact on both diagnosis and treatment outcomes. The discovery of novel biological indicators and metabolic dysregulation, can significantly rely on comprehension of the modified metabolism in cancer, is a research focus. Tissue histology is a critical feature in the diagnostic testing of many ailments, such as cancer. To assess the surgical margin of the tumour on patients, frozen section histology is a tedious, laborious, and typically arbitrary method. Concurrent monitoring of ion images in tissues facilitated by the latest advancements in mass spectrometry imaging (MSI) is far more efficient than optical tissue image analysis utilized in conventional histopathology examination. This article focuses on the "desorption electrospray ionization (DESI)-MSI" technique's most recent advancements and uses in cancer research. DESI-MSI can provide wealthy information based on the variances in metabolites and lipids in normal and cancerous tissues by acquiring ion images of the lipid and metabolite variances on biopsy samples. As opposed to a systematic review, this article offers a synopsis of the most widely employed cutting-edge DESI-MSI techniques in cancer research.

Recent Advances of MALDI-Mass Spectrometry Imaging in Cancer Research

For several decades, cancer has been the primary cause of mortality worldwide. New diagnosis and regimens have been developed to improve the chemotherapeutic efficacy and the quality of life of the patients. However, cancer tissues are complex and difficult to assess. Understanding the various properties of the tumor and its environment is crucial for cancer and pharmaceutical research. Several analytical techniques have been providing new insights into cancer research. Recently, matrix-assisted laser desorption ionization (MALDI)-mass spectrometry imaging (MSI), an advanced analytical technique, has been applied to translational research. Proteomic and lipidomic profiling obtained by MALDI-MSI has been critical for biomarker discovery and for monitoring heterogenous tumor tissues. In this review, we discuss technical approaches, benefits and recent applications of MALDI-MSI as a valuable tool in cancer research, namely for diagnosis, therapy, prognosis.

Preclinical PET, SPECT, CT, MRI and optical imaging in cancer research: An overview

Cancer research is primarily dependent on rodent models. There has been a huge advancement in anticancer drug discovery in the last two decades, which is mainly due to improved animal models and introduction of non-invasive imaging technologies. Non-invasive imaging technology plays an important role in cancer and other biomedical research areas including neurology, cardiology, nanotechnology and stem cell biology. The intricate pathways in cancer initiation, progression and metastasis can be visualized and the processes can be analyzed quantitatively using these techniques. Robust preclinical data is the backbone of anticancer drug discovery, which can be obtained precisely using imaging technology. This review is focused on the dedicated preclinical imaging modalities such as Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), X-ray Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Optical imaging and Cerenkov imaging. This paper discusses their present roles in basic and translational research towards evaluation of suitability of target molecules for further clinical trials.The unique features of the imaging modalities enable them to provide information necessary for understanding structural, functional and molecular processes involved in various stages of cancer development thus bridging the gap between bench and bedside.

Mass Spectrometry Imaging in Cancer Research: Future Perspectives.

In the last decade mass spectrometry imaging has developed rapidly, in terms of multiple new instrumentation innovations, expansion of target molecules, and areas of application. Mass spectrometry imaging has already had a substantial impact in cancer research, uncovering biomolecular changes associated with disease progression, diagnosis, and prognosis. Many new approaches are incorporating the use of readily available formalin-fixed paraffin-embedded cancer tissues from pathology centers, including tissue blocks, biopsy specimens, and tumor microarrays. It is also increasingly used in drug formulation development as an inexpensive method to determine the distributions of drugs and their metabolites. In this chapter, we offer a perspective in the current and future methodological developments and how these may open up new vistas for cancer research.

Quantitative multimodality imaging in cancer research and therapy.

Advances in hardware and software have enabled the realization of clinically feasible, quantitative multimodality imaging of tissue pathophysiology. Earlier efforts relating to multimodality imaging of cancer have focused on the integration of anatomical and functional characteristics, such as PET-CT and single-photon emission CT (SPECT-CT), whereas more-recent advances and applications have involved the integration of multiple quantitative, functional measurements (for example, multiple PET tracers, varied MRI contrast mechanisms, and PET-MRI), thereby providing a more-comprehensive characterization of the tumour phenotype. The enormous amount of complementary quantitative data generated by such studies is beginning to offer unique insights into opportunities to optimize care for individual patients. Although important technical optimization and improved biological interpretation of multimodality imaging findings are needed, this approach can already be applied informatively in clinical trials of cancer therapeutics using existing tools. These concepts are discussed herein.

Abstract 3925: Optical coherence tomography imaging in cancer research.

Abstract Optical coherence tomography (OCT) is an established imaging technology with a greater than 10 year history in the clinic. Over the past 5 years, an increasing number of cancer investigators have employed OCT in preclinical studies and have found that its unique capabilities address some of the gaps left by existing intravital imaging approaches. However, because OCT is relatively new to the cancer research community, these capabilities and limitations are not broadly known. Therefore, to facilitate translation, we will summarize OCT to the cancer research community. This will include a description of how it works, what its capabilities are, and what its role in preclinical cancer research is now and what it is likely to become over the next decade. The basic principles of OCT will be summarized to allow investigators to compare it with alternative imaging technologies and identify investigations where OCT is best suited. The imaging modes of OCT will be described and examples of use in cancer investigations will be given. The use of OCT for angiography at spatial and temporal scales not accessible to other technologies will be described. We will also present anatomical imaging of tumors using OCT and highlight its ability to assess tumor volume and to map tumor viability. Finally, the advantages of OCT-based label-free lymphangiography will be described and compared with existing approaches for lymphatic vessel imaging. We will end our discussion by communicating briefly some of the innovations in OCT that are happening now in research and engineering laboratories and the new capabilities that such innovations are likely to enable. Through this presentation, we hope to establish dialogues to drive technology development toward answering critical problems in cancer research. Citation Format: Benjamin J. Vakoc, Dai Fukumura, Timothy P. Padera, Rakesh K. Jain, Brett E. Bouma. Optical coherence tomography imaging in cancer research. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3925. doi:10.1158/1538-7445.AM2013-3925

Semiconductor Quantum Dots for Biomedicial Applications

Semiconductor quantum dots (QDs) are nanometre-scale crystals, which have unique photophysical properties, such as size-dependent optical properties, high fluorescence quantum yields, and excellent stability against photobleaching. These properties enable QDs as the promising optical labels for the biological applications, such as multiplexed analysis of immunocomplexes or DNA hybridization processes, cell sorting and tracing, in vivo imaging and diagnostics in biomedicine. Meanwhile, QDs can be used as labels for the electrochemical detection of DNA or proteins. This article reviews the synthesis and toxicity of QDs and their optical and electrochemical bioanalytical applications. Especially the application of QDs in biomedicine such as delivering, cell targeting and imaging for cancer research, and in vivo photodynamic therapy (PDT) of cancer are briefly discussed.

Advancers in Optical Imaging in Cancer Research — Part 2

TCRT continues to offer to its readers the current advances in OPTICAL BIOPSY. This special section’s focus is presented in four articles in optical imaging area. The salient features of the articles touch upon the use of time and frequency domain in imaging, the use of different wavelengths of several of possible fingerprint molecules in cancer, the role of hypoxia in cancer, the use of key topical contrast agent with confocal micro-endoscope, and the use of ultrasound guided hybrid system with optical diffusive tomography for minima invasive cancer detection. Several key methods are discussed in these articles. Ueda’s group (1) presents clinical results on breast cancer screening using multi-channel Time Resolved optical spectroscopy system in the development of optical mammography. Time-correlated single photon counting and Ti Sapphire laser beam irradiated the breasts. 3D images of breast were reconstructed using the time-resolved paths and algorithms. More than 200 breast cancer patients participated in the study. Piao’s group (2) present imaging using frequency domain methods; in particular, DC approach with several wavelengths in optical diffusive optical tomography probing key finger print molecules of hemoglobin, oxyhemoglobin and water for imaging cancer regions. Zhu’s group (3) combined ultrasound with diffusive optical tomography commonly called DOT by Britton Chance for mapping hypoxia region of tumors. The fingerprints molecules are hemoglobin and oxyhemoglobin concentration in blood phantoms and in vivo cancer patients. The article from Kortum’s group (4) discussed on the use and efficacy of topical fluorescent contrast agent and miroenedoscopy for detection of Barrett’s neoplastic regions in 26 patients at 206 sites .The morphologic and metabolic features of gastrointestinal neoplastic lesions were delineated. The next issue of TCRT will be a continuation of articles in Optical Imaging Advances in cancer area – part 2.

Advances in Optical Imaging in Cancer Research – Part 1

TCRT continues to offer to its readers the current advances in OPTICAL BIOPSY. This special section’s focus is presented in four articles in optical imaging area. The salient features of the articles touch upon the use of time and frequency domain in imaging, the use of different wavelengths of several of possible fingerprint molecules in cancer, the role of hypoxia in cancer, the use of key topical contrast agent with confocal micro-endoscope, and the use of ultrasound guided hybrid system with optical diffusive tomography for minima invasive cancer detection. Several key methods are discussed in these articles. Ueda’s group (1) presents clinical results on breast cancer screening using multi-channel Time Resolved optical spectroscopy system in the development of optical mammography. Time-correlated single photon counting and Ti Sapphire laser beam irradiated the breasts. 3D images of breast were reconstructed using the time-resolved paths and algorithms. More than 200 breast cancer patients participated in the study. Piao’s group (2) present imaging using frequency domain methods; in particular, DC approach with several wavelengths in optical diffusive optical tomography probing key finger print molecules of hemoglobin, oxyhemoglobin and water for imaging cancer regions. Zhu’s group (3) combined ultrasound with diffusive optical tomography commonly called DOT by Britton Chance for mapping hypoxia region of tumors. The fingerprints molecules are hemoglobin and oxyhemoglobin concentration in blood phantoms and in vivo cancer patients. The article from Kortum’s group (4) discussed on the use and efficacy of topical fluorescent contrast agent and miroenedoscopy for detection of Barrett’s neoplastic regions in 26 patients at 206 sites .The morphologic and metabolic features of gastrointestinal neoplastic lesions were delineated. The next issue of TCRT will be a continuation of articles in Optical Imaging Advances in cancer area – part 2.

In search of the Holy Grail: Folate-targeted nanoparticles for cancer therapy

Targeted drug therapy or “smart” drug delivery, potentially combined with simultaneous imaging modalities to monitor the delivery of drugs to specific tissues, is arguably the “holy grail” of pharmacology. Therapeutic approaches that exploit nanoparticles to deliver drugs selectively to cancer cells are currently considered one of the most promising avenues in the area of cancer therapeutics and imaging. The potential to deliver active chemotherapeutic drugs in the vicinity or directly within specific tumors via receptor mediated pathways, and to image tumors through the use of nanoparticles has been conceptually and experimentally shown for several classes of nanoparticles. Nanoparticles functionalized with the vitamin folic acid are of particular interest as a variety of malignant tumors are known to overexpress the folate receptor(s). Indeed, several nanoparticle architectures with improved retention time, administration route, biocompatibility, absorption, and clearance are being proposed and are in late stage clinical development. This commentary highlights some of the most important concepts related to nanoparticles and folate-mediated drug delivery and imaging in cancer research.

High-throughput small animal PET imaging in cancer research: evaluation of the capability of the Inveon scanner to image four mice simultaneously

The aim of this study was to assess the capability of small animal PET (SA-PET) devices to image four mice simultaneously to improve the throughput of SA-PET experiments in cancer research. A customized bed was designed to image up to four mice simultaneously. This bed can easily replace the bed provided by the manufacturer and is connected to an anaesthesia device. A mouse-sized phantom was imaged, mimicking simultaneous imaging of four mice with computation of recovery coefficients and spillover ratios (SORs). In addition, eight mice bearing subcutaneous tumours (human embryonal carcinoma, n=22 tumours) were simultaneously imaged in groups of four on an Inveon SA-PET scanner after injection of F-fluoro-D-glucose. Tumour activity (Bq/ml), as determined by the SA-PET, was compared with ex-vivo counting. For a 5-mm rod, recovery coefficients were 1.15 and 1.05 for a phantom imaged at the central field of view or off-centred on the customized bed, respectively. SORair and SORwater were 0.05 and 0.04 for a phantom imaged alone and 0.15 and 0.06 for a phantom imaged with three additional scatter sources, respectively. Correlation between SA-PET and ex-vivo quantification was good (r=0.91, P<0.0001). The mean ratio of PET quantitative data and ex-vivo counting was equal to 0.9 (95% confidence interval: 0.70-1.09). New generation SA-PET may be suitable for simultaneously imaging four tumour-bearing mice, although improvement in scatter correction efficiency appears necessary. The type of customized bed developed in this study could be easily adapted to other large-bore SA-PET scanners.

TU‐C‐201C‐04: Informatics Infrastructure for Quantitative Assessment of Cancer Treatment Response

There have been substantial advances in creating novel imaging platforms and quantitative imaging methods to provide accurate information about the status of patients with cancer. Quantitative imaging biomarkers promise improved sensitivity in assessing cancer treatment response and in identifying new therapeutics. These methods have tremendous potential to improve the accuracy and efficiency of cancer research; however, the lack of software infrastructure to enable validating and adopting these methods in cancer clinical trials hampers progress. Validating and using new quantitative imaging techniques is hindered by several challenges: (1) lack of tools to record quantitative imaging information about tumor burden reproducibly and efficiently in the clinical workflow; (2) lack of coordination and effective communication between oncologists and radiologists in making quantitative imaging assessments; (3) lack of integration of multiple different quantitative measures of tumor burden that, when taken together, would be more informative than individual indicators, and (4) lack of infrastructure to enable sharing of data derived from quantitative imaging methods among centers and data mining.We are tackling these challenges with the goal of enabling cancer researchers to reproducibly measure tumor burden, to better assess the effectiveness of therapies in patient cohorts, potentially leading to shorter clinical trials, and to make the best treatment choices for individual cancer patients. Our work, being conducted as one of the research centers in NCI's new Quantitative Imaging Network (QIN), has four objectives: (1) to develop software infrastructure to harmonize data collection and analysis across different image viewing platforms, (2) to create tools leveraging caBIG technologies that permit comprehensive and reproducible assessment of the quantitative imaging features of tumor burden, and that will improve the coordination of radiologists and oncologists in collecting quantitative image data, (3) to develop methods to analyze quantitative image data to provide decision support, helping oncologists to evaluate and recognize whether a treatment is effective, and (4) to evaluate the utility of this infrastructure in prospective clinical trials, thereby demonstrating improvement in researchers' ability to assess response to treatment in patient cohorts and in individual patients. As a result of this work, the oncology community will be able to share approaches to validating and standardizing imaging biomarkers and quantitative imaging measurements of tumor responses to cancer therapies, which in turn will lead to robust comparison of quantitative methods and to the identification of more accurate approaches for assessing tumor response. Ultimately, this work will enable translational research, accelerating incorporation of quantitative imaging methods into cancer research and improving patient care.Learning Objectives:1. Understand the opportunity and current limitations of quantitative imaging in cancer research.2. Learn about new developments in imaging informatics to improve quantitative image‐based assessment of cancer treatment response.3. Recognize future opportunities of imaging informatics to use quantitative imaging for assessing new cancer therapies, optimizing treatment decisions, and personalizing patient care.

Primer on Imaging Technologies for Cancer

Medical images represent maps of the spatial distribution of tissue properties. Each modality probes a specific set of tissue properties such as x-ray attenuation for computed tomography, transmission of sound for ultrasound, and the rate of glucose uptake for fluorodeoxyglucose-positron emission tomography. Understanding the basic principal underlying each modality is important for developing approaches to utilize imaging in cancer research and clinical care. In addition, each modality has specific challenges related to reliable quantitation that are important to appreciate.

Multimodality Imaging

Noninvasive “multimodal” in vivo imaging is not just becoming standard practice in the clinic, but is rapidly changing the evolving field of experimental imaging of genetic expression (“molecular imaging”). The development of multimodality methodology based on nuclear medicine (NM), positron emission tomography (PET) imaging, magnetic resonance imaging (MRI), and optical imaging is the single biggest focus in many imaging and cancer centers worldwide and is bringing together researchers and engineers from the far-ranging fields of molecular pharmacology to nanotechnology engineering. The rapid growth of in vivo multimodality imaging arises from the convergence of established fields of in vivo imaging technologies with molecular and cell biology. The cross-pollination of these disciplines has been accelerated in part by the establishment of the National Institutes of Health NCI P20 and P50 awards, for example, and by the sheer potential of the technology. Multimodality imaging is widely considered to involve the incorporation of two or more imaging modalities, usually within the setting of a single examination using, for example, dual- or triple-labeled optical or nuclear medicine “reporter” agents or by performing ultrasound or optical studies within the MR, single-photon emission computed tomography (SPECT), or x-ray computed tomography (CT) environment. Clinically, the best example of multimodality imaging is seen in the rapid evolution of PET-SPECT and PET-CT scanner hybrids. The PET modality has developed into perhaps the most used “multimodal” imaging method. The incorporation of PET into single, hybrid, and multimodality units to provide functional (typically from injected F-18DG studies) and anatomic information is becoming extremely popular,1–2 so much so that, for example, PET/CT hybrids can be found in outpatient screening centers located in shopping malls. The role of any multimodal imaging …

Current advances in molecular imaging: noninvasive in vivo bioluminescent and fluorescent optical imaging in cancer research.

Recently, there has been tremendous interest in developing techniques such as MRI, micro-CT, micro-PET, and SPECT to image function and processes in small animals. These technologies offer deep tissue penetration and high spatial resolution, but compared with noninvasive small animal optical imaging, these techniques are very costly and time consuming to implement. Optical imaging is cost-effective, rapid, easy to use, and can be readily applied to studying disease processes and biology in vivo. In vivo optical imaging is the result of a coalescence of technologies from chemistry, physics, and biology. The development of highly sensitive light detection systems has allowed biologists to use imaging in studying physiological processes. Over the last few decades, biochemists have also worked to isolate and further develop optical reporters such as GFP, luciferase, and cyanine dyes. This article reviews the common types of fluorescent and bioluminescent optical imaging, the typical system platforms and configurations, and the applications in the investigation of cancer biology.

Current Advances in Molecular Imaging: Noninvasive In Vivo Bioluminescent and Fluorescent Optical Imaging in Cancer Research

Recently, there has been tremendous interest in developing techniques such as MRI, micro-CT, micro-PET, and SPECT to image function and processes in small animals. These technologies offer deep tissue penetration and high spatial resolution, but compared with noninvasive small animal optical imaging, these techniques are very costly and time consuming to implement. Optical imaging is cost-effective, rapid, easy to use, and can be readily applied to studying disease processes and biology in vivo. In vivo optical imaging is the result of a coalescence of technologies from chemistry, physics, and biology. The development of highly sensitive light detection systems has allowed biologists to use imaging in studying physiological processes. Over the last few decades, biochemists have also worked to isolate and further develop optical reporters such as GFP, luciferase, and cyanine dyes. This article reviews the common types of fluorescent and bioluminescent optical imaging, the typical system platforms and configurations, and the applications in the investigation of cancer biology.

Magnetic resonance imaging in cancer research

Non-invasive assessment of antineoplastic response and correlation of the location, magnitude and duration of transgene expression in vivo would be particularly useful for evaluating cancer gene therapy protocols. This review presents selected examples of how magnetic resonance (MR) has been used to assess therapeutic efficacy by non-invasive quantitation of cell kill, to detect a therapeutic response prior to a change in tumour volume and to detect spatial heterogeneity of the tumour response and quantitate transgene expression. In addition, applications of the use of bioluminescence imaging (BLI) for the evaluation of treatment efficacy and in vivo transgene expression are also presented. These examples provide an overview of areas in which imaging of animal tumour models can contribute towards improving the evaluation of experimental therapeutic agents.

SIMS ion microscopy as a novel, practical tool for subcellular chemical imaging in cancer research

The development of cryogenic sample preparations, subcellular image quantification schemes, and correlative confocal laser scanning microscopy and ion microscopy have made dynamic SIMS a versatile tool in biology and medicine. For example, ion microscopy can provide much needed, novel information on calcium influx and intracellular calcium stores at organelle resolution in normal and transformed cells in order to better understand the altered calcium signaling in malignant cells. 3-D SIMS imaging of cells revealed dynamic gradients of calcium in cells undergoing mitosis and cytokinesis. Studies of subcellular localization of anticancer drugs is another area of research where ion microscopy can provide novel observations in many types of cancers. Ion microscopy is already an essential tool in boron neutron capture therapy (BNCT) of brain cancer as it can be used to quantitatively image the subcellular location of boron in cells and tissues. This information is critically needed for testing the efficacy of boronated agents and for calculations of radiation dosimetry.