Development Of Molecular Imaging Agents Research Articles

A Novel Dual-labeled Peptide for Multimodal Imaging of EGFR with L858R Mutation.

The development of molecular imaging agents targeting epidermal growth factor receptor (EGFR) with L858R mutation may help with the selection of non-small cell lung carcinoma (NSCLCL) patients who may benefit from EFGR tyrosine kinase inhibitor (TKI) therapy. In this study, we developed 99mTc STHHYYP-GHEG-ECGK-tetramethylrhodamine (STHHYYP-ECGK-TAMRA) to target EGFR with L858R mutation in NSCLC tumors and verified its probability as a molecular imaging agent. Fmoc solid-phase peptide synthesis was used to synthesize STHHYYP-ECGKTAMRA. 99mTc labelled STHHYYP-ECGK-TAMRA was prepared. Gamma imaging, fluorescent imaging and biodistribution were performed in murine models bearing NCI-H1975 and NCI-H1650 tumors. The binding affinity value (Kd) of 99mTc STHHYYP-ECGK-TAMRA was estimated to be 130.6 ± 29.2 nM in NCI-H1975 cells. The gamma camera images showed a substantial uptake of 99mTc STHHYYP-ECGK-TAMRA in the NCI-H1975 tumor. The % injected dose/gram of the NCI-H1975 tumor tissue was 2.77 ± 0.70 and 3.48 ± 1.01 at 1 and 3 h, respectively. Specific binding of 99mTc STHHYYP-ECGK-TAMRA to L858R-mutated EGFRpositive NCI-H1975 cells and tumors was demonstrated in in vivo and in vitro studies. The results suggest that 99mTc STHHYYP-ECGK-TAMRA is a good candidate agent for dualmodality imaging targeting EGFR with L858R mutation.

Imaging Biomarkers for Monitoring the Inflammatory Redox Landscape in the Brain.

Inflammation is one key process in driving cellular redox homeostasis toward oxidative stress, which perpetuates inflammation. In the brain, this interplay results in a vicious cycle of cell death, the loss of neurons, and leakage of the blood–brain barrier. Hence, the neuroinflammatory response fuels the development of acute and chronic inflammatory diseases. Interrogation of the interplay between inflammation, oxidative stress, and cell death in neurological tissue in vivo is very challenging. The complexity of the underlying biological process and the fragility of the brain limit our understanding of the cause and the adequate diagnostics of neuroinflammatory diseases. In recent years, advancements in the development of molecular imaging agents addressed this limitation and enabled imaging of biomarkers of neuroinflammation in the brain. Notable redox biomarkers for imaging with positron emission tomography (PET) tracers are the 18 kDa translocator protein (TSPO) and monoamine oxygenase B (MAO–B). These findings and achievements offer the opportunity for novel diagnostic applications and therapeutic strategies. This review summarizes experimental as well as established pharmaceutical and biotechnological tools for imaging the inflammatory redox landscape in the brain, and provides a glimpse into future applications.

Mistiming Death: Modeling the Time-Domain Variability of Tumor Apoptosis and Implications for Molecular Imaging of Cell Death.

Apoptosis, in the context of cancer, is a form of programmed cell death induced by chemotherapy, radiotherapy, and immunotherapy. As this is a central pathway in treatment response, considerable effort has been expended on the development of molecular imaging agents to non-invasively measure tumor apoptosis prior to quantitative changes in tumor dimensions. Despite these efforts, clinical trials directed at imaging apoptosis by PET, SPECT, and MRI have failed to robustly predict response to treatment with high sensitivity and specificity. Although these shortcomings may be linked to probe design, we propose that the combination of variability in the timing of maximal in vivo tumor apoptosis and sub-optimal sampling times fundamentally limits the predictive power of PET/SPECT apoptosis imaging. Herein, we surveyed the literature describing the time course of therapy-induced tumor apoptosis in vivo and used these data to construct a mathematical model describing the onset, duration, amplitude, and variability of the apoptotic response. Uncertainty in the underlying time of initiation of tumor apoptosis was simulated by Gaussian, uniform, and Landau distributions centered at the median time-to-maximum apoptotic rate derived from the literature. We then computationally sampled these models for various durations to simulate PET/SPECT imaging agents with variable effective half-lives. Models with a narrow Gaussian distribution of initiation times for tumor apoptosis predicted high contrast ratios and strong predictive values for all effective tracer half-lives. However, when uncertainty in apoptosis initiation times were simulated with uniform and Landau distributions, high contrast ratios and predictive values were only obtained with extremely long imaging windows (days). The imaging contrast ratios predicted in these models were consistent with those seen in pre-clinical apoptosis PET/SPECT imaging studies and suggest that uncertainty in the timing of tumor cell death plays a significant role in the maximal contrast obtainable. Moreover, when uncertainty in both apoptosis initiation and imaging start times were simulated, the predicted contrast ratios were dramatically reduced for all tracer half-lives. These studies illustrate the effect of uncertainty of apoptosis initiation on the predictive power of PET/SPECT apoptosis imaging agents and suggest that long integration times are required to surmount uncertainty in the time domain of this biological process.

A Decade's Progress in the Development of Molecular Imaging Agents Targeting the Growth Hormone Secretagogue Receptor.

The growth hormone secretagogue receptor 1a (GHSR), also called the ghrelin receptor, is a G protein-coupled receptor known to play an important metabolic role in the regulation of various physiological processes, including energy expenditure, growth hormone secretion, and cell proliferation. This receptor has been implicated in numerous health issues including obesity, gastrointestinal disorders, type II diabetes, and regulation of body weight in patients with Prader-Willi syndrome, and there has been growing interest in studying its mechanism of behavior to unlock further applications of GHSR-targeted therapeutics. In addition, the GHSR is expressed in various types of cancer including prostate, breast, and testicular cancers, while aberrant expression has been reported in cardiac disease. Targeted molecular imaging of the GHSR could provide insights into its role in biological processes related to these disease states. Over the past decade, imaging probes targeting this receptor have been discovered for the imaging modalities PET, SPECT, and optical imaging. High-affinity analogues of ghrelin, the endogenous ligand for the GHSR, as well as small molecule inhibitors have been developed and evaluated both in vitro and in pre-clinical models. This review provides a comprehensive overview of the molecular imaging agents targeting the GHSR reported to the end of 2019.

High-Throughput Approaches to the Development of Molecular Imaging Agents.

Molecular imaging allows for the visualization of changes at the cellular level in diseases such as cancer. A successful molecular imaging agent must rely on disease-selective targets and ligands that specifically interact with those targets. Unfortunately, the translation of novel target-specific ligands into the clinic has been frustratingly slow with limitations including the complex design and screening approaches for ligand identification, as well as their subsequent optimization into useful imaging agents. This review focuses on combinatorial library approaches towards addressing these two challenges, with particular focus on phage display and one-bead one-compound (OBOC) libraries. Both of these peptide-based techniques have proven successful in identifying new ligands for cancer-specific targets and some of the success stories will be highlighted. New developments in screening methodology and sequencing technology have pushed the bounds of phage display and OBOC even further, allowing for even faster and more robust discovery of novel ligands. The combination of multiple high-throughput technologies will not only allow for more accurate identification, but also faster affinity maturation, while overall streamlining the process of translating novel ligands into clinical imaging agents.

Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared – non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

Targeting Tumor Hypoxia in Radiotherapy: A Brief Review of Historical Background and Recent Progress

Tumor hypoxia is a physiologic barrier to radiotherapy and anti-tumor drug delivery. Numerous efforts have been made to overcome this barrier and to improve therapeutic outcomes. Strategies for targeting tumor hypoxia have included chemical radiosensitizers and hyperthermia, followed by combined synergic therapeutic modalities. Clinical hypoxia measurements and the development of molecular imaging agents prompted trials on dose escalation in external beam radiotherapy, which takes advantage of contemporary sophisticated radiation dose delivery techniques. Increases in our understanding of hypoxia-induced biological pathways have led to the investigation of various hypoxia targeting drugs. Radiolabeled hypoxia targeting drugs deliver radionuclides into hypoxic tumor cells and achieve highly localized cell death. In this manuscript, we briefly review the methods of targeting tumor hypoxia in radiotherapy. These include image guided dose escalation in external beam radiotherapy, radiosensitizers, and radiolabeled agents targeting hypoxia pathways and the receptors on hypoxic tumor cells. Our current understanding of tumor hypoxia is the culmination of the collective efforts of generations of researchers. New frontiers are continuing to expand, as new discoveries are being made on both the macroscopic and molecular levels.

Synthesis and evaluation of technetium-99m-labeled bioreductive pharmacophores conjugated with amino acids and peptides for tumor imaging.

Development of molecular imaging agents to target tumor has become a major trend in nuclear medicine. With the aim to develop new potential 99mTc-radiopharmaceuticals for targeting tumor, we have synthesized 5-nitroimidazolyl amino acids and RGD-coupled 2-nitroimidazoles. Technetium-99m radiolabeling with high radiochemical purity (>90%) was achieved for all the compounds. The radiolabeled complexes exhibited substantial in vitro stability in saline, serum, and histidine solution (10(-2) m). Cell binding studies in EAC and B16F10 cell lines also revealed rapid and comparatively high cellular internalization. Among all the compounds studied, the binding of 99mTc(CO)3-5 to B16F10 cells was moderately inhibited by the competitive peptide c[RGDfV], suggesting specificity of the radioligand toward αvβ3 receptor. However, no significant displacement of bound radioligand was observed when the binding of the 99mTc-labeled complexes to above cells was challenged with excess competitive peptide. Fluorescent microscopy study provided direct evidence of intracellular localization of 5(6)-carboxyfluorescein-labeled 2-nitroimidazolyl-RGD-peptide in αvβ3-positive B16F10 mouse melanoma cell line. The ligands caused only 8-13% of hemolysis toward rat erythrocytes at concentrations as high as 100 μm. Imaging and biodistribution studies were performed in Swiss albino mice bearing induced tumor. 99mTc-1 and 99mTc(CO)3-5 demonstrated a very favorable in vivo profile. Selective uptake and retention in tumor with encouraging tumor/muscle and tumor/blood ratio and significant cellular uptake of fluorescence-labeled-2-nitroimidazolyl RGD indicate the great potentiality of the pharmacophore for further evaluation as potential molecular imaging agent in cancer diagnosis.

Multivalent viral capsids with internal cargo for fibrin imaging.

Thrombosis is the cause of many cardiovascular syndromes and is a significant contributor to life-threatening diseases, such as myocardial infarction and stroke. Thrombus targeted imaging agents have the capability to provide molecular information about pathological clots, potentially improving detection, risk stratification, and therapy of thrombosis-related diseases. Nanocarriers are a promising platform for the development of molecular imaging agents as they can be modified to have external targeting ligands and internal functional cargo. In this work, we report the synthesis and use of chemically functionalized bacteriophage MS2 capsids as biomolecule-based nanoparticles for fibrin imaging. The capsids were modified using an oxidative coupling reaction, conjugating ∼90 copies of a fibrin targeting peptide to the exterior of each protein shell. The ability of the multivalent, targeted capsids to bind fibrin was first demonstrated by determining the impact on thrombin-mediated clot formation. The modified capsids out-performed the free peptides and were shown to inhibit clot formation at effective concentrations over ten-fold lower than the monomeric peptide alone. The installation of near-infrared fluorophores on the interior surface of the capsids enabled optical detection of binding to fibrin clots. The targeted capsids bound to fibrin, exhibiting higher signal-to-background than control, non-targeted MS2-based nanoagents. The in vitro assessment of the capsids suggests that fibrin-targeted MS2 capsids could be used as delivery agents to thrombi for diagnostic or therapeutic applications.

Molecular Imaging of Alzheimer Disease Pathology

Development of molecular imaging agents for fibrillar β-amyloid positron-emission tomography during the past decade has brought molecular imaging of Alzheimer disease pathology into the spotlight. Large cohort studies with longitudinal follow-up in cognitively normal individuals and patients with mild cognitive impairment and Alzheimer disease indicate that β-amyloid deposition can be detected many years before the onset of symptoms with molecular imaging, and its progression can be followed longitudinally. The utility of β-amyloid PET in the differential diagnosis of Alzheimer disease is greatest when there is no pathologic overlap between 2 dementia syndromes, such as in frontotemporal lobar degeneration and Alzheimer disease. However β-amyloid PET alone may be insufficient in distinguishing dementia syndromes that commonly have overlapping β-amyloid pathology, such as dementia with Lewy bodies and vascular dementia, which represent the 2 most common dementia pathologies after Alzheimer disease. The role of molecular imaging in Alzheimer disease clinical trials is growing rapidly, especially in an era when preventive interventions are designed to eradicate the pathology targeted by molecular imaging agents.

Abstract IA12: Issues in the development of molecular imaging agents for cancer imaging: An observation from the MICAD editors

Abstract Significant progress in the development of molecular imaging agents has been made during the past decade. However, the translation of the imaging agents from the laboratory to the clinic is rather slow, which can be attributed to several factors such as multidisciplinary effort requirement, stringent regulations, and economic consideration. To enhance the investigation in molecular imaging and facilitate the bench-to-bedside translation, NIH launched the Molecular Imaging and Contrast Agent Database (MICAD) in 2005, aiming to provide freely accessible online information regarding imaging probes and contrast agents. A comprehensive literature search by the MICAD editors shows that >5,000 imaging agents to date have been published and characterized in vitro and in animal models of human disease, and this number increases by 300-500 new agents every year. Majority of the agents have been developed for SPECT (~36%), PET (~30%), MRI (~17%), and optical imaging (~6.5%). On review of the published data, the MICAD editors have observed that the agents are often inconsistently or incompletely characterized, which makes it difficult to evaluate, validate, and meta-analyze the data generated from different studies of imaging agents. To address this issue, the MICAD editors have proposed several guidelines for the characterization of imaging agents developed for MRI, PET/SPECT, and optical imaging, respectively. The guidelines summarize the essential parameters that are required to characterize imaging agents from synthesis, physicochemical properties, in vitro cellular studies, to animal studies. It is worth pointing out that it is more challenging to develop imaging agents that are specific to the tumor cells with metastatic capability. Most sensitive biomarkers are developed for the primary and advanced tumors, but few are reliable and specific for the metastatic tumor cells. It can be difficult to uncover the discordance in biological processes between the primary and disseminated tumor cells. The spatial resolution of images is sufficient to reveal whether a metastatic lesion is positive for a biomarker, but it is insufficient to delineate the spatial heterogeneity within a lesion. Furthermore, most imaging probes provide an assessment of the temporal and spatial expression distribution of a biomarker, which is not necessarily a read-out of the target activity although “smart” probes have been reported. Because of the multidisciplinary nature of molecular imaging and the limitations of the techniques used to capture the data, there is no single set of parameters that is suitable to define the properties of the various types of imaging agents. It is essential to ensure that these agents meet certain quality control parameters at the preclinical stage so that they can be used without delay for clinical studies. Citation Format: Liang Shan. Issues in the development of molecular imaging agents for cancer imaging: An observation from the MICAD editors. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr IA12.

Characterization of nanoparticle-based contrast agents for molecular magnetic resonance imaging

The development of molecular imaging agents is currently undergoing a dramatic expansion. As of October 2011, ~4,800 newly developed agents have been synthesized and characterized in vitro and in animal models of human disease. Despite this rapid progress, the transfer of these agents to clinical practice is rather slow. To address this issue, the National Institutes of Health launched the Molecular Imaging and Contrast Agents Database (MICAD) in 2005 to provide freely accessible online information regarding molecular imaging probes and contrast agents for the imaging community. While compiling information regarding imaging agents published in peer-reviewed journals, the MICAD editors have observed that some important information regarding the characterization of a contrast agent is not consistently reported. This makes it difficult for investigators to evaluate and meta-analyze data generated from different studies of imaging agents, especially for the agents based on nanoparticles. This article is intended to serve as a guideline for new investigators for the characterization of preclinical studies performed with nanoparticle-based MRI contrast agents. The common characterization parameters are summarized into seven categories: contrast agent designation, physicochemical properties, magnetic properties, in vitro studies, animal studies, MRI studies, and toxicity. Although no single set of parameters is suitable to define the properties of the various types of contrast agents, it is essential to ensure that these agents meet certain quality control parameters at the preclinical stage, so that they can be used without delay for clinical studies.

Trifunctional99mTc based radiopharmaceuticals: metal-mediated conjugation of a peptide with a nucleus targeting intercalator

The development of molecular imaging agents with multiple functions has become a major trend in radiopharmaceutical chemistry. We present herein the syntheses of trifunctional compounds, combining an acridine orange (AO) based intercalator with a GRP receptor specific bombesin like peptide (BBN). Metal-mediated conjugation of these two functions via the [2 + 1] approach to the third function, the [M(CO)(3)](+) (M = (99m)Tc, Re) moiety, yielded the final trifunctional molecules. The strongly fluorescent acridine orange, a nuclear targeting agent, has been derivatised with 4-imidazolecarboxylate as a bidentate ligand and bombesin with an isonitrile group as a monodentate ligand. For cell and nuclear uptake studies, [Re(L(1)-BBN)(L(2)-Ical)(CO)(3)] type complexes were synthesized and characterized. For radiopharmaceutical purposes, the (99m)Tc analogues have been prepared in a stepwise synthesis. Fluorescence microscopy studies on PC-3 cells, bearing the BBN receptor, showed high and rapid uptake into the cytoplasm. For the bifunctional molecule, lacking the BBN peptide, no internalization was observed.

Correlation Between Epidermal Growth Factor Receptor-Specific Nanobody Uptake and Tumor Burden: A Tool for Noninvasive Monitoring of Tumor Response to Therapy

Nanobodies represent an interesting class of probes for the generic development of molecular imaging agents. We studied the relationship between tumor uptake of the epidermal growth factor receptor (EGFR)-specific nanobody (99m)Tc-7C12 and tumor burden and evaluated the possibility of using this probe to monitor tumor response to erlotinib. The specificity and affinity of (99m)Tc-7C12 was determined on A431 cells. Cells expressing firefly luciferase were used to evaluate tumor burden using bioluminescence imaging. We evaluated the effect of erlotinib on tumor burden and (99m)Tc-7C12 uptake in vitro as well as in vivo. In vivo bioluminescence imaging was performed followed by pinhole single-photon emission computed tomography/micro-computed tomography. (99m)Tc-7C12 binds specifically to the receptor with high affinity (3.67 ± 0.59 nM). Erlotinib reduced tumor uptake and cell viability in a concentration-dependent manner. Tumor uptake of (99m)Tc-7C12 showed good correlation with tumor burden. Erlotinib treatment resulted in a progressive reduction of tumor burden and tumor uptake of (99m)Tc-7C12. (99m)Tc-7C12 binds to EGFR with high affinity and specificity. Tumor uptake is correlated with tumor burden. Quantification of (99m)Tc-7C12 uptake is promising for monitoring therapy response of EGFR-expressing tumors.

Molecular imaging agents: impact on diagnosis and therapeutics in oncology

Imaging has become a crucial tool in oncology throughout the course of disease detection and management, and is an integral part of clinical trials. Anatomical and functional imaging led the way, providing valuable information used in the diagnosis of disease, including data regarding the size and location of the tumour and on physiological processes such as blood flow and perfusion. As understanding of cancer pathogenesis has advanced through the identification of genetic, biochemical and cellular alterations in evolving tumours, emphasis has been put on developing methods to detect and serially monitor such alterations. This class of approaches is referred to as molecular imaging. Molecular imaging offers the potential for increasingly sensitive and specific visualisation and quantification of biological processes at the cellular and molecular level. These approaches have become established as essential tools for cancer research, early cancer detection and staging, and monitoring and predicting response to targeted therapies. Here, we discuss recent advances in the development of molecular imaging agents and their implementation in basic cancer research as well as in more rationalised approaches to cancer care.

Phage display and molecular imaging: expanding fields of vision in living subjects

In vivo molecular imaging enables non-invasive visualization of biological processes within living subjects, and holds great promise for diagnosis and monitoring of disease. The ability to create new agents that bind to molecular targets and deliver imaging probes to desired locations in the body is critically important to further advance this field. To address this need, phage display, an established technology for the discovery and development of novel binding agents, is increasingly becoming a key component of many molecular imaging research programs. This review discusses the expanding role played by phage display in the field of molecular imaging with a focus on in vivo applications. Furthermore, new methodological advances in phage display that can be directly applied to the discovery and development of molecular imaging agents are described. Various phage library selection strategies are summarized and compared, including selections against purified target, intact cells, and ex vivo tissue, plus in vivo homing strategies. An outline of the process for converting polypeptides obtained from phage display library selections into successful in vivo imaging agents is provided, including strategies to optimize in vivo performance. Additionally, the use selections are performed against pre-defined targets, the use of cell lines, tissue, and in vivo homing selections have also been valuable. These latter strategies avoid the need to identify a specific target at the outset, allow library selections under conditions potentially more relevant to a clinical setting, and can lead to the discovery of unanticipated and interesting targets. The full potential of phage display is far from being completely explored; many library formats and selection strategies have not been fully exploited for the production of molecular imaging agents. The successful and rapid translation of phage-derived molecular imaging agents into the clinic remains a challenge, but new methods and tools are becoming available for optimizing in vivo performance. In conclusion, phage display will continue to be a significant driving force and a key player in enabling in vivo molecular imaging to deliver on its promise for both basic science and clinical applications.

Molecular Imaging and Magnetic Resonance Imaging in Early Diagnosis of Alzheimer's Disease

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. Magnetic resonance (MR) or computed tomography (CT) imaging is recommended for routine evaluation of dementias. The development of molecular imaging agents and the new techniques of MR for AD are critically important for early diagnosis, neuropathogenesis studies and assessing treatment efficacy in AD. Neuroimaging using nuclear medicine techniques such as SPECT, PET and MR spectroscopy has the potential to characterize the biomarkers for Alzheimer's disease. The present review summarizes the results of radionuclide imaging and MR imaging in AD.

Multimodality Cardiovascular Molecular Imaging, Part I

In Part I of this consensus article, the imaging methodology, evolving imaging technology, and development of novel targeted molecular probes relevant to the developing field of cardiovascular molecular imaging were reviewed. Novel reporter gene and reporter probe imaging approaches for tracking of cardiac transgene expression were also discussed and have important future implications for evaluation of gene- and cell-based therapies for the failing heart. The current role of metabolic and receptor imaging was also briefly reviewed, as these represent the beginning of our clinical application of molecular imaging within the cardiovascular system. Part II will summarize the available targeted imaging probes as well as specific future applications of molecular imaging for identification and evaluation of critical pathophysiological processes of the cardiovascular system.

Development of Alzheimer's disease imaging agents for clinical studies

Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive loss of neurotransmitters, as well as acetylcholinesterase and nicotinic acetylcholine receptors in the central nervous system that leads to learning and memory deficits, among other problems. The disease is associated with increased production and accumulation extracellular amyloid plaques and neurofibrillary tangles in aging human brain, shown in postmortem exams. New methods for reliable in vivo measurement of brain therefore would be much more ideal. PET and SPECT imaging are sensitive methods for the quantitation of AD biomarkers. The development of molecular imaging agents for AD is critically important in the early diagnosis, neuropathogenesis studies and treatment of AD. A number of potential diagnostic PET and SPECT imaging agents targeting AD have been synthesized and evaluated. Although many agents showed excellent results for in vitro monitoring of the disease, there are only several radioligands with high selectivity and specificity to binding sites and appropriate pharmacokinetics, such as [11C]MP4A, [11C]PMP, [11C]nicotine, 2- or 6-[18F]fluoro-A-85380, [11C]SB-13, [11C]PIB, and [18F]FDDNP, that have been tested in AD patients. Here we review some recent progress and development of AD imaging agents using PET and SPECT in human clinical studies.

Molecular imaging: novel tools in visualizing rheumatoid arthritis

Molecular imaging is a rapidly emerging field in biomedical research, aiming at the visualization, characterization and quantification of molecular and cellular processes non-invasively within intact living organisms. To sense biological processes such as gene expression, angiogenesis, apoptosis or cell trafficking in vivo, imaging reporter agents that interact specifically with molecular targets and appropriate imaging systems are currently under development. In rheumatoid arthritis, these novel tools will be used to evaluate physiological and pathophysiological processes, to facilitate diagnosis and monitor therapeutic regimens, to enable reliable prognosis and to support the development of new therapies. In this review, we summarize the basic principles of molecular imaging, such as the development of molecular imaging agents, the actual capabilities of different imaging modalities and the most recent advances in molecular imaging, demonstrating the potential of this technology. With regard to their applicability in rheumatic diseases, we discuss potential molecular targets, current experimental approaches and the future prospects for molecular imaging in rheumatoid arthritis.