Complementary molecular imaging technologies: High resolution SPECT, PET and MRI (original) (raw)

Molecular imaging with SPECT as a tool for drug development

Advanced Drug Delivery Reviews, 2011

Molecular imaging techniques are increasingly being used as valuable tools in the drug development process. Radionuclide-based imaging modalities such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have proven to be useful in phases ranging from preclinical development to the initial stages of clinical testing. The high sensitivity of these imaging modalities makes them particularly suited for exploratory investigational new drug (IND) studies as they have the potential to characterize in vivo pharmacokinetics and biodistribution of the compounds using only a fraction of the intended therapeutic dose (microdosing). This information obtained at an early stage of clinical testing results in a better selection among promising drug candidates, thereby increasing the success rate of agents entering clinical trials and the overall efficiency of the process. In this article, we will review the potential applications of SPECT imaging in the drug development process with an emphasis on its applications in exploratory IND studies.

The Role of PET/CT and SPECT/CT in Oncology Drug Development

Understanding the hallmarks of cancer is valuable in advancing drug development to fight the disease. With the advent of molecular imaging, non-invasive in vivo visualization of physiology and functional pathways allow for multiple levels of disease and therapy assessment beyond tumor size measurements offered by conventional anatomic scans. Radiolabeling targeted molecules can provide insight into tumor interactions within the body and may help guide therapeutic constructs. Traditionally, radiolabeled probes have been useful for staging and diagnosis but they can also be created to monitor and identify drug targets and pharmaceutical biodistribution among other novel approaches. Radiotracers can be imaged either through single photon emission computed tomography (SPECT) or positron emission tomography (PET), with advantages and limitations to both. Adding CT to either modality is an added benefit for anatomic localization and attenuation correction. In this review, we will briefly discuss several molecular imaging agents, which target metabolism (18F-FDG, 18F-FACBC, 11C acetate), proliferation (18F-FLT, 18F-5FU, 18F-FdCyd), and cancer specific drug receptors (111In-morab009, 111In-trastuzumab, 89Zr-panutumumab). Molecular imaging is a powerful tool that one day, may be employed to personalize treatment and dosing strategies and predict anticancer therapy outcomes.

Molecular Imaging Aided Improvement in Drug Discovery and Development

The current drug discovery and development platform is rapidly expanding with new classes of pharmaceuticals and novel biological information. The drug discovery and development process relies on the utilization of relevant and robust tools, methods, and models that are predictive of clinical effects in terms of diagnosis, prevention, therapy and prognosis. One of the methods that have gained prominence over the years is Molecular Functional Imaging that optimizes and ensures delivery, measures efficacy and toxicity of the therapeutic agents to the target cell or site in pre-clinical setting. Currently three different imaging modalities that include Radionuclide Imaging (Positron Emission Tomography or PET and Single Photon Emitted Computed Tomography or SPECT), Magnetic Resonance Imaging (MRI) and Optical Imaging (Bioluminescence and Florescence) are being extensively used in preclinical models to assess the pharmacokinetics, functional alteration of target and other sites and efficacy of treatment. These real time monitoring modalities are promoting development of novel and sophisticated molecular technologies to identify modulators of protein-protein interactions, apoptosis, protease actions and various other physiological responses. In parallel, significant paradigm shift is occurring at drug discovery and development landscape through emergence of several drug delivery systems like hydrogels, polymers, liposomes and nanoparticles. These innovative delivery vehicles are the future of modern personalized medicine which is still in experimental phases. Molecular Imaging techniques are again the final validation tools for determining the safety, efficacy and need of further improvement of these delivery vehicles. In this review we discuss the current and evolving state of drug discovery and development aided by functional molecular imaging techniques.

The role of molecular imaging in modern drug development

Drug Discovery Today, 2014

Drug development represents a highly complex, inefficient and costly process. Over the past decade, the widespread use of nuclear imaging, owing to its functional and molecular nature, has proven to be a determinant in improving the efficiency in selecting the candidate drugs that should either be abandoned or moved forward into clinical trials. This helps not only with the development of safer and effective drugs but also with the shortening of time-to-market. The modern concept and future trends concerning molecular imaging will assumedly be hybrid or multimodality imaging, including combinations between high sensitivity and functional (molecular) modalities with high spatial resolution and morphological techniques.

Microdosing, Imaging Biomarkers and SPECT: A Multi-Sided Tripod to Accelerate Drug Development

Current Pharmaceutical Design, 2009

The advances of nuclear medicine imaging instrumentation and radiopharmaceutical sciences allow their involvement in the developmental processes of therapeutic drugs. New chemical entities, meant as potential drugs, need to comply with the proof-of-principle. Tomographic imaging methods as PET, SPECT and CT have been used for small animal and human studies at an early stage of drug development. Using a drug candidate in a radiolabeled form in obtaining quantitative imaging data provides opportunity for a complete morphological and functional overview of targeting properties and overall pharmacokinetics. This can be helpful in go/ no-go decision making. Microdosing, using e.g.1% of the proposed dose of the radiolabeled potential drug plays an important part in this early development and notably reduces the risk of serious adverse effects in human volunteers or patients. This paper primarily focuses on the way in which microdosing and SPECT imaging may contribute to the development of drugs. Furthermore, this paper illustrates how these techniques may help to eliminate weak drug candidates at early stage, making time and funds available for potential lead compounds. Eventually this approach facilitates and accelerates new drug approval. The present paper highlights how these techniques make drug development easier in the field of oncology and neurology.

Pharmaco-imaging in drug and biologics development : fundamentals and applications

2014

The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade

International Journal of Molecular Sciences

Positron emission tomography (PET) uses radioactive tracers and enables the functional imaging of several metabolic processes, blood flow measurements, regional chemical composition, and/or chemical absorption. Depending on the targeted processes within the living organism, different tracers are used for various medical conditions, such as cancer, particular brain pathologies, cardiac events, and bone lesions, where the most commonly used tracers are radiolabeled with 18F (e.g., [18F]-FDG and NA [18F]). Oxygen-15 isotope is mostly involved in blood flow measurements, whereas a wide array of 11C-based compounds have also been developed for neuronal disorders according to the affected neuroreceptors, prostate cancer, and lung carcinomas. In contrast, the single-photon emission computed tomography (SPECT) technique uses gamma-emitting radioisotopes and can be used to diagnose strokes, seizures, bone illnesses, and infections by gauging the blood flow and radio distribution within tissu...

Pharmaco-Imaging in Drug and Biologics Development

Springer eBooks, 2014

The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein.

Positron emission tomography (PET): expanding the horizons of oncology drug development

Investigational new drugs, 2003

Positron emission tomography (PET) allows three-dimensional quantitative determination of the distribution of radioactivity permitting measurement of physiological, biochemical, and pharmacological functions at the molecular level. Until recently, no method existed to directly and noninvasively assess transport and metabolism of neoplastic agents as a function of time in various organs as well as in the tumor. Standard preclinical evaluation of potential anticancer agents entails radiolabeling the agent, usually with tritium or 14C, sacrifice experiments, and high-performance liquid chromatography (HPLC) analysis to determine the biodistribution and metabolism in animals. Radiolabeling agents with positron-emitting radionuclides allows the same information to be obtained as well as in vivo pharmacokinetic (PK) data by animal tissue and plasma sampling in combination with PET scanning. In phase I/II human studies, classic PK measurements can be coupled with imaging measurements to de...