DOI:10.1259/bjr/13675329

出版商:British Institute of Radiology    

年代:2003

数据来源: WILEY

DOI:10.1259/bjr/25833499

出版商:British Institute of Radiology    

年代:2003

数据来源: WILEY

摘要:

Molecular imaging – the exploitation of specific molecules as the source of image contrast – promises new insights into disease processes in the laboratory and since the imaging modalities employed are applicable clinically, can be used to translate this knowledge into new diagnostics and treatments in the clinic. This brief review focuses on the use of MR-based molecular imaging techniques for developing tumour therapy. As examples, methods for detecting drug-induced tumour cell apoptosis; the response of tumours and their susceptibilities to an antivascular drug; early signs of tumour immune rejection and methods for detecting immune cell infiltration of tumours are described.

DOI:10.1259/bjr/50577981

出版商:British Institute of Radiology    

年代:2003

数据来源: WILEY

摘要:

MRI provides unsurpassed soft tissue contrast, but the inherent low sensitivity of this modality has limited the clinical use to imaging of water protons. With hyperpolarization techniques, the signal from a given number of nuclear spins can be raised more than 100 000 times. The strong signal enhancement enables imaging of nuclei other than protons,e.g.13C and15N, and their molecular distributionin vivocan be visualized in a clinically relevant time window. This article reviews different hyperpolarization techniques and some of the many application areas. As an example, experiments are presented where hyperpolarized13C nuclei have been injected into rabbits, followed by rapid13C MRI with high spatial resolution (scan time<1 s and 1.0 mm in-plane resolution). The high degree of polarization thus enabled mapping of the molecular distribution within various organs, a few seconds after injection. The hyperpolarized13C MRI technique allows a selective identification of the molecules that give rise to the MR signal, offering direct molecular imaging.

DOI:10.1259/bjr/26631666

出版商:British Institute of Radiology    

年代:2003

数据来源: WILEY

摘要:

Studies of pharmacokinetics (which is what the body does to the drug) and pharmacodynamics (which is what the drug does to the body) are essential components of the modern process of cancer drug discovery and development. Defining the precise relationship between pharmacokinetics and pharmacodynamics is critical. It is especially important to establish a well understood pharmacological “audit trail” that links together all of the essential parameters of drug action, from the molecular target to the clinical effects. The pharmacological audit trail allows us to answer two absolutely crucial questions: (1) how much gets there; and (2) what does it do? During the pre-clinical drug discovery phase, it is essential that pharmacokinetic/pharmacodynamic (PK/PD) properties are optimized, so that the best candidate can be selected for clinical development. As part of contemporary mechanistic, hypothesis-testing clinical trials, construction of the pharmacological PK/PD audit trail facilitates rational decision-making. However, PK/PD endpoints frequently require invasive sampling of body fluids and tissues. Non-invasive molecular measurements,e.g.using MRI or spectroscopy, or positron emission tomography, are therefore very attractive. This review highlights the need for PK/PD endpoints in modern drug design and development, illustrates the value of PK/PD endpoints, and emphasises the importance of non-invasive molecular imaging in drug development. Examples cited include the use of PK/PD endpoints in the development of molecular therapeutic drugs such as the Hsp90 molecular chaperone inhibitor 17AAG, as well as the development of SR-4554 as a non-invasive probe for the detection of tumour hypoxia.

DOI:10.1259/bjr/27373639

出版商:British Institute of Radiology    

年代:2003

数据来源: WILEY

摘要:

Ultrasound has received less attention than other imaging modalities for molecular imaging, but has a number of potential advantages. It is cheap, widely available and portable. Using Doppler methods, flow information can be obtained easily and non-invasively. It is arguably the most physiological modality, able to image structure and function with less sedation than other modalities. This means that function is minimally disturbed, and multiple repeat studies or the effect of interventions can easily be assessed. High frame rates of over 200 frames a second are achievable on current commercial systems, allowing for convenient cardiac studies in small animals. It can be used to guide interventional or invasive studies, such as needle placement. Ultrasound is also unique in being both an imaging and therapeutic tool and its value in gene therapy has received much recent interest. Ultrasound biomicroscopy has been used forin uteroimaging and can guide injection of virus and cells. Ultrahigh frequency ultrasound can be used to determine cell mechanical properties. The development of microbubble contrast agents has opened many new opportunities, including new functional imaging methods, the ability to image capillary flow and the possibility of molecular targeting using labelled microbubbles.

DOI:10.1259/bjr/57063872

出版商:British Institute of Radiology    

年代:2003

数据来源: WILEY

DOI:10.1259/bjr/16098061

出版商:British Institute of Radiology    

年代:2003

数据来源: WILEY

DOI:10.1259/bjr/22322389

出版商:British Institute of Radiology    

年代:2003

数据来源: WILEY