Kam Leung

Molecular Imaging and Contrast Agent Database (MICAD): Evolution and Progress

The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; www.micad.nlm.nih.gov) to students, researchers, and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, X-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1,000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4,250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration as well as a comma separated values file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, pre-clinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities, and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments, or suggestions for further improvement of the database by writing to the editors at micad@nlm.nih.gov.

Important parameters to consider for the characterization of PET and SPECT imaging probes

The Molecular Imaging and Contrast Agents Database (MICAD; http://www.micad.nih.gov) is mandated to provide freely accessible online information regarding molecular imaging probes and contrast agents (called tracer, probe or agent from here on) that are under development, in preclinical or clinical evaluation, or commercially available for clinical application [1]. The primary aim of MICAD is to promote the discovery, development and application of molecular imaging in biology, drug discovery and the clinical sciences. For inclusion in MICAD, the primary consideration is that a molecular imaging probe should have in vivo animal or human studies published in peer-reviewed journals available on the PubMed database. A comprehensive search on PubMed showed there were ∼4500 imaging and contrast agents published as of November 2010 and N200 agents are added to the list every year. The information on each agent in MICAD is obtained from original publications in scientific journals, patents, books, etc., and is summarized in a book chapter format by the editors. A single chapter is compiled for each agent and this involves screening information from a few (e.g., for new or novel agents) to hundreds of publications [e.g., for probes and agents that are in clinical trials or are approved by the United States Food and Drug Administration (FDA) for clinical use in the US]. As of now, there are N1000 chapters in MICAD and members of the imaging community are encouraged to become Guest Authors for the database [1]. During the process of compiling the various chapters published in MICAD, the editors have observed that sometimes important basic chemical and biological infor-

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.

Essential parameters to consider for the characterization of optical imaging probes

The Molecular Imaging and Contrast Agents Database (MICAD) was launched in 2005 to promote the development and application of imaging and contrast agents (probes) to advance the field of molecular imaging. As of March 2012, there are approximately 1170 agents available in MICAD. Based on the modality used for imaging, the largest category of probes described in MICAD are those used for PET (41.6%), followed by agents used for single-photon emission computed tomography (30.3%), optical imaging (12.0%), MRI (9.3%), multimodality imaging (3.4%), ultrasound (2.4%) and x-ray/computed tomography (1.0%). This article is intended to be a guideline for new investigators and students who wish to characterize an optical imaging probe that will be used to perform in vivo molecular imaging studies. It is necessary, however, to ensure that these agents meet certain quality control parameters before they are used in various in vitro and in vivo applications.

Clinical use of gadobutrol for contrast-enhanced magnetic resonance imaging of neurological diseases

Correspondence: Kam Leung Molecular Imaging and Contrast Agents Database, National Center for Biotechnology Information, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894, USA Tel +1 301 402 6747 Fax +1 301 480 4637 Email leung@mail.nih.gov Abstract: Contrast-enhanced magnetic resonance imaging (CE-MRI) is an important clinical tool for diagnosing neurological diseases. The appropriate use of a suitable MRI contrast agent or contrast pharmaceutical is essential for CE-MRI to produce desirable diagnostic images. Currently, there are seven contrast agents (CAs) or pharmaceuticals approved for clinical imaging of the central nervous system (CNS) in the US, Europe, or Japan. All of the clinically approved CAs are water-soluble gadolinium-based contrast agents (GBCAs) which do not penetrate the CNS blood–brain barrier (BBB). These agents are used for imaging CNS areas without a BBB, or various pathologies, such as tumors and infection that break down the BBB and allow CAs to enter into the surrounding parenchyma. Clinically, GBCAs are most useful for detecting primary and secondary cerebral neoplastic lesions. Among these CNS GBCAs, gadobutrol (Gd-BTDO3A, GadovistTM) is a neutral, nonionic, macrocyclic compound that showed promising results from clinical trials of CNS imaging. In comparison with other GBCAs, Gd-BT-DO3A has relatively high in vitro kinetic stability and r 1 relaxivity. Gd-BT-DO3A has been recently approved by the US Food and Drug Administration (FDA) in 2011 for CNS imaging. A review of available literature shows that Gd-BT-DO3A exhibits similar safety and clinical efficacy profiles to other GBCAs. Gd-BT-DO3A has the distinguishing feature that it is the only clinical agent commercially available in a formulation of 1.0 M concentration with a relatively higher in vitro T 1 shortening per unit volume than other clinical GBCAs which are only available in 0.5 M concentration. This double concentration of Gd-BT-DO3A may allow a relatively higher concentration of the agent to localize in the CNS and produce a better contrast enhancement at the same clinical dose as other GBCAs. Several recent published multicenter clinical trials appeared to support this potential advantage of Gd-BT-DO3A.