Molecular imaging with PET and SPECT is a very promising methodology for the drug development because it can directly visualize the spatiotemporal distribution and interaction processes of drugs in human at the molecular level using an appropriate molecular probe. The molecular probes used in these studies include a drug radiolabeled isotopically, a dosage form incorporated a radionuclide, and a radiolabeled ligand interacted with a targeted molecule, such as receptors, transporters and enzymes. The development of these radiolabeled molecular probes requires a rational design based on the structure-biological activity-biodistribution relationship. This paper describes the concept and several examples of the drug design of molecular probes used for PET/SPECT molecular imaging for drug development research.

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In recent several years, the drug targeting methodology has been actively applied to MRI contrast agents, particularly to “selective MRI contrast agents” that can only enhance image contrasts at target sites. This situation is one part of reflection of fusion between DDS and molecular imaging fields. This review describes how and for what purpose drug targeting can be applied to developments of novel MRI contrast agents. This review is composed of the following contents;concept of selective MRI contrast agents, methodological differences between the targetings of drugs and contrast agents, mechanisms of selective contrasts, and the authors' study of polymeric micelle MRI contrast agents.

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Biological imaging techniques have been advanced with the development of imaging systems and corresponding imaging probes. Among the systems, positron emission tomography(PET), an imaging system by using extremely short half-life positron-emitters, is considered as one of the most sensitive imaging modality. PET has been used for functional imaging in clinical diagnostic field as well as that in research purpose. In vivo molecular imaging of the drug candidates can be used for the analysis of their distribution properties in a living body. To accelerate the development of DDS mediated medicines, in vivo imaging technology for determining the behavior of nanoparticles and for nanomedicines would be useful.
We have studied on the trafficking of various kinds of liposomes by use of PET, and, recently, we have developed a rapid and easy positron-labeling methodology for DDS nanoparticles. In this review, we introduce the modality of in vivo molecular imaging for the development of DDS medicine and discuss the prospects of the technology.

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In vivo molecular imaging has become a key technology for drug development and pathophysiological science. Recently, Japanese Government also initiated the Molecular Imaging Research Program under MEXT. We are mostly utilizing PET(positron emission tomography) as a first-choice modality, because of its ultra-high sensitivity for molecules, adequate temporal and spatial resolution, and especially broad spectrum of target molecules. The present status for development of PET molecular probes, instrumentations including microPET, and the methods for quantitative analyses will be introduced with some examples.
In vivo molecular imaging could bring the high-quality information about:
(1) Molecular diagnosis for living patients with symptoms
(2) Closer approach for etiology and differential diagnosis
(3) Direct follow-up of key molecules as disease markers
(4) DDS, Pharmacokinetics/Pharmacodynamics in experimental animals/primates/human
(5) Dose finding information for individuals, corresponding to SNP's
(6) Direct evidence for accumulation in non-target organs:Related to adverse effects
(7) Drug effects with surrogate markers
(8) Early decision of dropout substances (drug candidates)
In 2005, RIKEN and National Institute of Radiological Science were selected as the key centers for development of all-Japan research network to further promote mutual international and multi-disciplinary collaboration on in vivo molecular imaging. The concept, project themes, and our achievements so far are described.

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MRI has provided high tissue contrast and spatial resolution non-invasively and is widely used in the clinical field. High field MR imaging, which provides a high signal-to-noise ratio and frequency resolution, is expected to allow imaging of specific molecular-events. Examples include the efficiency of drug development, visualization of regeneration or migration treatment, and oncology or neuroscience research and diagnostics. Drug delivery systems are a key technology for the application of MRI to “molecular MR imaging”.

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