Use Of Imaging Agents Research Articles

A case of laparoscopic sigmoidectomy using thermography for colonic blood flow assessment

BackgroundIndocyanine green (ICG) fluorescence imaging is widely used in gastrointestinal surgery and is considered useful for reducing anastomotic leakage; however, because ICG remains in the tissue for a certain amount of time, we occasionally must re-evaluate colonic blood flow over a short time period during surgery. Herein, we verify the usefulness of thermography (TG) for evaluating colonic blood flow in a patient who underwent a laparoscopic sigmoidectomy for sigmoid colon cancer.Case presentationThe patient is 43-year-old man who underwent laparoscopic resection of the sigmoid colon for colon cancer. After vascular treatment of the colonic mesentery, ICG/TG identified the boundary between ischemic and non-ischemic colon tissues. An additional 2 cm of colonic mesentery was resected because of the presence of a diverticulum noted at the intended site of oral anastomosis when attaching the anvil head. After additional vascular treatment of the colonic mesentery and administration of ICG, fluorescence was observed in the colon; however, TG identified the zone of the temperature transition on the surface of the colonic mesentery, even after additional colonic mesentery resection in the same region as previously observed. This zone was used as the cut-off line. There were no complications, such as anastomotic leakage, after the surgery.ConclusionAlthough accumulation of similar cases is necessary, TG has the potential for use as an auxiliary diagnostic tool in clinical practice. TG can depict the presence or absence of blood flow based on surface temperature without the use of imaging agents, and is inexpensive and easy to perform.

Drug-loaded PEG-PLGA nanoparticles for cancer treatment.

Nanoparticles based on single-component synthetic polymers, such as poly (lactic acid-co-glycolic acid) (PLGA), have been extensively studied for antitumor drug delivery and adjuvant therapy due to their ability to encapsulate and release drugs, as well as passively target tumors. Amphiphilic block co-polymers, such as polyethylene glycol (PEG)-PLGA, have also been used to prepare multifunctional nanodrug delivery systems with prolonged circulation time and greater bioavailability that can encapsulate a wider variety of drugs, including small molecules, gene-targeting drugs, traditional Chinese medicine (TCM) and multi-target enzyme inhibitors, enhancing their antitumor effect and safety. In addition, the surface of PEG-PLGA nanoparticles has been modified with various ligands to achieve active targeting and selective accumulation of antitumor drugs in tumor cells. Modification with two ligands has also been applied with good antitumor effects, while the use of imaging agents and pH-responsive or magnetic materials has paved the way for the application of such nanoparticles in clinical diagnosis. In this work, we provide an overview of the synthesis and application of PEG-PLGA nanoparticles in cancer treatment and we discuss the recent advances in ligand modification for active tumor targeting.

SNMMI Clinical Trials Network Research Series for Technologists: Clinical Research Primer- Use of Imaging Agents in Therapeutic Drug Development and Approval.

The process of bringing a new drug to market is complex and has recently necessitated a new drug discovery paradigm for the pharmaceutical industry that is both more efficient and more economical. Key to this has been the increasing use of nuclear medicine and molecular imaging to support drug discovery efforts by answering critical questions on the pathway for development and approval of a new therapeutic drug. Some of these questions include: (i) Does the new drug reach its intended target in the body at sufficient levels to effectively treat or diagnose disease without unacceptable toxicity? (ii) How is the drug absorbed, metabolized, and excreted? (iii) What is the effective dose in humans? To conduct the appropriate imaging studies to answer such questions, pharmaceutical companies are increasingly partnering with molecular imaging departments. Nuclear medicine technologists are critical to this process as they perform scans to collect the qualitative and quantitative imaging data used to measure study endpoints. This article describes preclinical and clinical research trials and provides an overview of the different ways that radiopharmaceuticals are used to answer critical questions during therapeutic drug development.

SNMMI Clinical Trials Network Research Series for Technologists: Introduction.

The field of nuclear medicine and molecular imaging has grown tremendously over the past several years with the approval of new imaging agents, diagnostic radiopharmaceuticals, and radiopharmaceutical therapies. Clinical research continues to expand within nuclear medicine and molecular imaging departments. Working as a nuclear medicine technologist on a clinical trial or with investigational radiopharmaceuticals can be quite different from working in an approved-drug setting in the clinic. Nuclear medicine technologists involved in clinical trials can be at the front line of following rigorous trial requirements and ensuring good-quality data. The details of working in clinical research are often not taught in nuclear medicine technologist programs. As such, there is an emerging need for education about clinical research for both experienced and new nuclear medicine technologists, particularly for those working with investigational radiopharmaceuticals. This article is an introduction to the SNMMI Clinical Trials Network Research Series for Technologists. This series of articles aims to provide education on working in the context of a clinical trial within the nuclear medicine department. The following 7 topics will be addressed in the series: ethical issues in clinical research, application of good clinical practice to clinical research in medical imaging, contract research organizations with application in clinical imaging, a clinical research primer on the regulatory process for how and when radiopharmaceuticals can be used and the role of the institutional review board, use of imaging agents in therapeutic drug development and approval, imaging agent trials, and imaging agents with radiopharmaceutical therapies in clinical trials. Other topics may be added over the course of the development of the series.

Design of a ligand for cancer imaging with long blood circulation and an enhanced accumulation ability in tumors.

The use of imaging agents to visualize tumor cells is an advantageous technique to achieve a more efficient intraoperative diagnosis and effective debulking operations. Targeting of these agents to certain receptors that are overexpressed in cancer cells, such as the folate receptor, aids in tumor targeting. Several imaging probes have been developed using this strategy. However, these ligand-targeting cancer imaging probes are rapidly cleared during systemic delivery due to their small size, which compromises their biodistribution and circulation. Improving the detection of cancer requires higher accumulation and effective retention activities of imaging probes. Here we developed a new design for a folate-fluorophore conjugate that is modified with palmitoyl. Palmitic acid has a strong binding affinity with human serum albumin (HSA), which has the ability to form non-covalent host-guest complexes and has a blood half-life of 19 days. In this strategy, HSA is expected to serve as an endogenous nanocarrier for the designed probe in blood circulation. We hypothesized that via a reversible interaction with HSA, this simple palmitoyl modification on a folate-fluorophore conjugate can induce long blood circulation of the probe. Our folate-targeted probe could show longer blood circulation compared to the probe which lacks palmitoyl.

Synthetic methodology for asymmetric ferrocene derived bio-conjugate systems via solid phase resin-based methodology.

Early detection is a key to successful treatment of most diseases, and is particularly imperative for the diagnosis and treatment of many types of cancer. The most common techniques utilized are imaging modalities such as Magnetic Resonance Imaging (MRI), Positron Emission Topography (PET), and Computed Topography (CT) and are optimal for understanding the physical structure of the disease but can only be performed once every four to six weeks due to the use of imaging agents and overall cost. With this in mind, the development of "point of care" techniques, such as biosensors, which evaluate the stage of disease and/or efficacy of treatment in the clinician's office and do so in a timely manner, would revolutionize treatment protocols.1 As a means to exploring ferrocene based biosensors for the detection of biologically relevant molecules2, methods were developed to produce ferrocene-biotin bio-conjugates described herein. This report will focus on a biotin-ferrocene-cysteine system that can be immobilized on a gold surface.

Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

Investigation of gastric cancers in nude mice using X-ray in-line phase contrast imaging.

BackgroundThis paper is to report the new imaging of gastric cancers without the use of imaging agents. Both gastric normal regions and gastric cancer regions can be distinguished by using the principal component analysis (PCA) based on the gray level co-occurrence matrix (GLCM).MethodsHuman gastric cancer BGC823 cells were implanted into the stomachs of nude mice. Then, 3, 5, 7, 9 or 11 days after cancer cells implantation, the nude mice were sacrificed and their stomachs were removed. X-ray in-line phase contrast imaging (XILPCI), an X-ray phase contrast imaging method, has greater soft tissue contrast than traditional absorption radiography and generates higher-resolution images. The gastric specimens were imaged by an XILPCIs’ charge coupled device (CCD) of 9 μm image resolution. The PCA of the projective images’ region of interests (ROIs) based on GLCM were extracted to discriminate gastric normal regions and gastric cancer regions. Different stages of gastric cancers were classified by using support vector machines (SVMs).ResultsThe X-ray in-line phase contrast images of nude mice gastric specimens clearly show the gastric architectures and the details of the early gastric cancers. The phase contrast computed tomography (CT) images of nude mice gastric cancer specimens are better than the traditional absorption CT images without the use of imaging agents. The results of the PCA of the texture parameters based on GLCM of normal regions is (F1 + F2) > 8.5, but those of cancer regions is (F1 + F2) < 8.5. The classification accuracy is 83.3% that classifying gastric specimens into different stages using SVMs.ConclusionsThis is a very preliminary feasibility study. With further researches, XILPCI could become a noninvasive method for future the early detection of gastric cancers or medical researches.

Use of Imaging Agent to Determine Postoperative Indwelling Epidural Catheter Position

BackgroundEpidural anesthesia is widely used to provide pain relief, whether for surgical anesthesia, postoperative analgesia, treatment of chronic pain, or to facilitate painless childbirth. In many cases, however, the epidural catheter is inserted blindly and the indwelling catheter position is almost always uncertain.MethodsIn this study, the loss-of-resistance technique was used and an imaging agent was injected through the indwelling epidural anesthesia catheter to confirm the position of its tip and examine the migration rate. Study subjects were patients scheduled to undergo surgery using general anesthesia combined with epidural anesthesia. Placement of the epidural catheter was confirmed postoperatively by injection of an imaging agent and X-ray imaging.ResultsThe indwelling epidural catheter was placed between upper thoracic vertebrae (n = 83; incorrect placement, n = 5), lower thoracic vertebrae (n = 123; incorrect placement, n = 5), and lower thoracic vertebra-lumbar vertebra (n = 46; incorrect placement, n = 7). In this study, a relatively high frequency of incorrectly placed epidural catheters using the loss-of-resistance technique was observed, and it was found that incorrect catheter placement resulted in inadequate analgesia during surgery.ConclusionsAlthough the loss-of-resistance technique is easy and convenient as a method for epidural catheter placement, it frequently results in inadequate placement of epidural catheters. Care should be taken when performing this procedure.

Quantitative analysis of amyloid plaques in a mouse model of Alzheimer’s disease by phase-contrast X-ray computed tomography

Densely aggregated β-amyloid peptides are believed to play a key role in the pathogenesis of Alzheimer’s disease. Amyloid plaques are a potential target for molecular imaging to determine the clinical status of Alzheimer’s disease. Phase-contrast X-ray imaging combined with computed tomography is a promising technique that can be used to visualize the physical density of structures in biological tissues non-invasively, and without the use of imaging agents. Using brain tissue isolated from a mouse model of Alzheimer’s disease, we show that β-amyloid 40-positive/β-amyloid 42-positive amyloid plaques, but not β-amyloid 40-negative/β-amyloid 42-positive amyloid plaques, exist as high-density aggregates that can be specifically detected by phase-contrast X-ray computed tomography. The phase-contrast X-ray computed tomography detected β-amyloid 40-positive/β-amyloid 42-positive amyloid plaques in three-dimensions with an extremely high sensitivity comparable to that of histological analysis, and also enabled the load of amyloid plaques to be quantified. Furthermore, the use of phase-contrast X-ray computed tomography reveals that the physical density of β-amyloid 40-positive/β-amyloid 42-positive amyloid plaques increases with age, and that the large volume, high-density, amyloid plaques that are specifically observed in aged Alzheimer’s disease mice are closely associated with neuritic dystrophy. These results demonstrate that phase-contrast X-ray computed tomography is a highly sensitive imaging technique for analyzing dense-cored amyloid plaques in postmortem samples, and is beneficial in elucidating amyloid pathophysiology in Alzheimer’s disease.

Intelligent Biohybrid Materials for Therapeutic and Imaging Agent Delivery

Many molecular imaging techniques rely on tracer methods to visualize specific physiological processes in cells, animals, and humans. A new family of "smart" delivery systems for biomolecules has opened new opportunities for the molecular imaging field. One class of polymeric carriers reversibly become membrane destabilizing in response to sharp pH changes and were designed for delivering proteins and nucleic acids to intracellular compartments. These carriers could enable the use of imaging agents and intracellular reporters whose site of action made them previously inaccessible. A second class of stimuli-responsive polymer-biomolecule conjugates can be reversibly formed into particles of closely defined sizes. The ability to control when and where the protein or DNA species is in the free versus particle form may allow imaging applications that exploit their differential size and diffusion properties.

Reanalysis of cancer drugs: old drugs, new tricks.

Most cancer chemotherapy protocols in current use have been established empirically, and combination therapies have generally been designed based on single-agent activity and nonoverlapping toxicities. However, advances in our understanding of the molecular pathophysiology of human cancers indicate