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British Journal of Radiology (2003) 76, S98-S109
© 2003 British Institute of Radiology
doi: 10.1259/bjr/25833499
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Full Paper

Molecular imaging in vivo: an introduction

A S K Dzik-Jurasz, PhD, FRCS, FRCR

GlaxoSmithKline, 891–995 Greenford Road, Middlesex UB6 0HE, UK


   Introduction
Top
 Introduction
An approach to molecular...
 Specific examples of molecular...
 Nuclear magnetic resonance
 Translating molecular imaging to...
 Conclusion
 Declared interests
 References
 
The modern practice of medicine will soon be centred on the principles of molecular biology [1]. As a consequence technologies allowing precise, targeted and robotically delivered therapies will be needed to deliver this new practice. Significant stakeholders of this molecular approach are the pharmaceutical companies [2] and academia both of whom have committed substantial resources to targeted molecular therapies. In man the sequencing of the human genome [3, 4] has significantly facilitated this process and microarray analysis [5], bioinformatics [6] and high-throughput screening [7, 8] are providing additional insight into the molecular basis of disease.

Imaging will be a key resource in delivering the practice of molecular medicine. Biomedical imaging has already played a key role in defining many cellular and biochemical mechanisms [9]. The next phase in the development of molecular imaging (MI) requires the translation of a predominantly in vitro technology to an in vivo one. This will be achieved via a synthesis of chemistry, molecular biology and imaging hardware. Ultimately the aim should be the establishment of these practices in man.

MI therefore seeks to "image molecular events in vivo" [10] into which cell and mouse imaging are often added [11]. Although MI represents a new discipline rather than a new science its language remains unfamiliar to most imaging clinicians and scientists. Chemistry and molecular biology define the new vocabulary [12, 13]. The importance of MI should not be underestimated; the National Cancer Institute [14, 15] and National Institute of Health [16, 17] have strategically aligned themselves to its development and the teaching of the basics of MI to radiology residents is being advocated [18].


   An approach to molecular imaging
Top
 Introduction
 An approach to molecular...
Specific examples of molecular...
 Nuclear magnetic resonance
 Translating molecular imaging to...
 Conclusion
 Declared interests
 References
 
Length scales and sensitivity
Four to six orders of magnitude separate cellular and molecular events and cellular processes operate at nanomolar concentration. Small molecular weight compounds (<1000 D) typically have molecular radii of 10–10 m compared with a cell radius of 10–5 m. A clinical MR (magnetic resonance) scanner on the other hand has a spatial resolution of the order of 10–3 m. In respect of sensitivity, positron emission tomography (PET) is sensitive to 10–9 M whilst magnetic resonance spectroscopy (MRS) at clinical field strength is 10–4 M. Successful MI therefore requires probes with: (i) high affinity and specificity; (ii) the capability of overcoming biological delivery barriers; (iii) amplification strategies; and (iv) sensitive, fast and high resolution imaging techniques.

The molecular imaging "probe" concept
Molecular probes can be classified into three types [11] independent of imaging modality: (i) the compartmental probe; (ii) targeted probes; and (iii) "smart" sensor probes. Compartmental probes typically assess physiological parameters (i.e. flow and perfusion). In this case it is not the molecular process that is strictly being imaged but a surrogate. Targeted probes are composed directly against a specific moiety targeted to the molecule, receptor or enzyme of interest and an imaging component that provides the physical contrast. It is this specificity that makes the probe molecular and small molecules, peptides, enzyme substrates and antibodies have all been used in this manner. Finally, "smart" probes are agents designed to activate exclusively in the presence of their intended target. The absence of a significant background signal gives smart probes a significant signal advantage over simple targeted agents. A recent addition to this group includes nanosensors that detect oligonucleotide (DNA/RNA) pairings [19, 20].

Limitations and developments in the probe concept
A high specificity agent is useless if it cannot reach its target and limitations in delivery due to inherent biological barriers [21, 22] is an important issue for all imaging modalities. Possible solutions [11] include: (i) peptide membrane translocation signals; (ii) PEG-ylation; (iii) local delivery; and (iv) development of long circulating compounds that provides a more homogeneous distribution of agent. Having delivered the imaging agent there is then the issue of amplifying the signal. The sensitivity of detection of radionuclides gives these agents a considerable advantage over the other modalities. Amplification strategies [11] include: improving target concentration and probes that alter their physical behaviour through interaction with the target. These include agents that alter in relaxivity whilst much work has been done with fluorescence dequenching in optical imaging.


   Specific examples of molecular imaging – a modality-based approach
Top
 Introduction
 An approach to molecular...
 Specific examples of molecular...
Nuclear magnetic resonance
 Translating molecular imaging to...
 Conclusion
 Declared interests
 References
 
MI remains predominantly focused on pre-clinical disease models. Research has focused on imaging gene delivery, exogenous marker genes and the imaging of molecular pathways such as angiogenesis and apoptosis. Examples of molecular imaging approaches used by several common in vivo imaging modalities will now be discussed.


   Nuclear magnetic resonance
Top
 Introduction
 An approach to molecular...
 Specific examples of molecular...
 Nuclear magnetic resonance
Translating molecular imaging to...
 Conclusion
 Declared interests
 References
 
MRI has high spatial resolution but an inherently low signal yield necessitating signal amplification strategies [23]. In the field of angiogenesis, targeted agents against the {alpha}v{beta}3 integrin (these are transmembrane proteins involved in cell–cell adhesion) have demonstrated tumour neovasculature to advantage in a rabbit VX2 tumour [24]. In this strategy the targeting moiety was an engineered antibody against {alpha}v{beta}3 connected to a liposome carrying several Gd(III) moieties (in the form of chelates), which increased the relaxivity of the agent. Barrier penetration in this instance was less of an issue because the molecular target was de facto intravascular. Targeted agents have also been described against apoptotic markers [25] and transgene (Figure 1Go) products [26, 27].



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  		Figure 1. Demonstrating gene transfection using MRI. In this technique tumour cells were engineered to overexpress the transferrin receptor (a cell membrane receptor involved in regulating cellular iron uptake). As a result the tumour overexpressing transferrin receptors accumulated iron in the form of MIONs (monocrystalline iron oxide nanoparticles). The MIONs induce a high susceptibility (the left-hand tumour in these animals – the control tumour is on the right flank) imaged as signal loss by MR. The images were acquired on a 1.5 T system. Reproduced with permission [26].

 
Several "smart" MRI contrast agents have been described. Perhaps the best known is EgadMe [28] in which a galactopyranose ring is synthesised to protect a Gd(III) ion from bulk water (Figure 2Go). In the presence of expression of {beta}-galactosidase the ring is cleaved allowing access of bulk water molecules to the Gd(III). This same theme has been extended in the synthesis of a Ca2+ [29, 30] activated agent (Figure 3Go).



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  		Figure 2. In vivo use of a gadolinium based smart contrast agent to demonstrate gene transfection. When the enzyme {beta}-galactosidase is expressed in engineered cells, the {beta}-galactopyranose ring protecting the Gd3+ is cleaved allowing bulk water access to the paramagnetic gadolinium ion. The images labelled A and B are of Xenopus (African claw toed frog) embryos that express {beta}-galactosidase or not. The embryo labelled +mRNA is expressing {beta}-galactosidase and significantly more detail is seen in this embryo than the one labelled –mRNA. The bottom embryo is oriented upside down compared with the top one. Reproduced with permission [28].

 


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  		Figure 3. Example of a "smart" MRI probe. Ca2+ causes a conformational change in the molecule such that access of bulk water to the Gd3+ can be accessed or denied. Access of bulk water to the Gd3+ causes shortening in the longitudinal relaxation time of water protons and therefore signal enhancement on T1 imaging. Chemical structures courtesy of Prof. T Meade, NorthWestern University, USA.

 
MR techniques in cell imaging are also maturing [31]. In these studies cells of varying lineage are induced to take up iron oxides as superparamagnetic formulations. The imaging contrast results from the iron-induced susceptibility. Evidence to date suggests that the methodology is non-toxic and has single cell sensitivity at clinical field strength [32, 33]. It remains to be determined whether the T2* susceptibility approach or a T1 enhancement strategy will provide the greatest sensitivity to molecular events in vivo. It has been estimated recently that Gd(III) constructs with relaxivities in the order of 80 s–1 mM–1 require four to five times less atoms per cell than iron to elicit a detectable MR signal change [23, 34, 35].

MRS is a technique particularly suited to probing molecular events. The use of MRS is discussed later in this article but it should be noted that the technique has been used to demonstrate gene transfection. In particular gene transfection has been demonstrated in vivo using the cytosine deaminase [36] (Figure 4Go) or arginine kinase [37] paradigm.



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  		Figure 4. In vivo 19F-MRS (magnetic resonance spectroscopy) demonstration of gene transfection. In this example a tumour was grown on the flank of an animal the cells of which had been transfected with the cytosine deaminase (CD) gene (CD is a fungal gene and has no mammalian counterpart). CD catalyses the conversion of 5-fluorocytosine (5FC) into the active anticancer drug 5-fluorouracil (5FU). 5FU has a different resonant frequency to 5FC allowing its identification in vivo and confirming transfection with the CD gene. FNuc, Fluoronucleotides; FßAl, Fluoro-beta-alanine. Reproduced with permission [36].

 
CT
Although not as prevalent as clinical CT this modality has a role in molecular imaging. In comparison with PET and MR the installation of a small animal CT system is cheap. It has a resolution of the order of 50 µm, unlimited depth penetration and a fast scanning time (50 µm in plane resolution can be achieved in the order of several minutes compared with several hours via MR). Soft tissue tumours, bone and lung are best suited to study via CT. Small animal CT has been particularly avidly applied to phenotyping the myriad of knock in/out mice [11].

Ultrasound
Ultrasound has the advantage of real time imaging with down to 40 µm in plane resolution at 5 mm depth using 20–60 MHz probes. Bone and air artefacts notwithstanding ultrasound can be a useful technique when physiological information on flow is desirable. Recent developments in hardware and targeted agents have allowed ultrasound to translate to imaging molecular processes in vivo [38, 39]. The targeted agents are based on the same premise as other agents with the imaging contrast provided by microbubble technology. Improved sensitivity through the use of harmonic imaging [40] has additionally improved the signal to noise characteristics of ultrasound. An article dedicated to ultrasound in MI is provided in this special issue.

Positron emission tomography
PET is the current paradigm for sensitivity to molecular events with in vivo imaging [41]. Animal systems are now available providing 1–2 mm in plane resolution [11]. PET (and other radionuclide techniques) is ideally suited to imaging molecular events because of its sensitivity to biological amounts of compound (nano to femtomolar). The technique is limited by access to hardware. To take full advantage of PET radiochemistry requires ready access to a cyclotron (because the half-life of many radionuclides is in the order of minutes). Most importantly PET is quantitative [42] and provides the ability to characterize receptors and ligands at molecular concentrations [43]. PET is extensively used in the development of psychiatric [44, 45] and oncologic [46] drugs. A great strength in drug development is the ability to label a compound with the radionuclide isotope thereby maintaining its physicochemical properties (there would be little sense in labelling a putative therapeutic compound with a Gd(III) complex as this would so alter that compounds properties that it would be chemically unrecognisable). Examples of PET radionuclides used in molecular imaging include 15O (2.07 min), 13N (10 min), 11C (20.3 min), 18F (1.83 h), 124I (4.2 days) and 94Tcm (53 min).

PET radionuclides based on 18F such as 18F-flurothymidine (tumour proliferation) and 18F-fluorodeoxyglucose (glycolysis marker) have been particularly useful in probing neoplastic processes and are entering clinical research [47, 48]. Strictly speaking these are not specific molecular markers as they report on global cellular processes. Pre-clinically PET has been particularly useful in monitoring extracellular receptor expression and the efficacy of gene therapy vectors [49, 50]. Arguably, the paradigm for gene transfer imaging is the herpes simplex virus-thymidine kinase (HSV-Tk) system [51]. Thymidine kinase catalyses substrate phosphorylation, which becomes "trapped" intracellularly (Figure 5Go). If one of these substrates has an 18F substitution it is then possible to infer that HSV-Tk has been incorporated into the host genome by the persistence of radioactive counts over the region of interest. The sensitivity of PET to molecular events is perhaps best illustrated by the imaging of transcriptional regulation [52, 53] (Figure 6Go). Transciption (the process of transcribing DNA to mRNA) is a core mechanism in the cellular manufacture of proteins and is a common focal point of cellular disruption in cancer.



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  		Figure 5. Non-invasive demonstration of transfection of the herpes simplex virus thymidine kinase (HSV-Tk) gene into a murine tumour using PET. The C6tk+ tumour cells were transfected with HSV-Tk and implanted into nude mice. Control tumours had C6 cells only. HSV-Tk causes phosphorylation and intracellular trapping of the radiotracer 9-[(1-[18F]Fluoro-3-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG). Note persistence of activity in the C6tk+ tumour indicating gene transfection. Reproduced with permission [91].

 


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  		Figure 6. Non-invasive demonstration of protein–protein interactions using in vivo PET. The radiotracer [9-(4-[18F]Fluoro-3-hydroxymethylbutyl)guanine] is trapped inside tumour cells that bind p53 and TAg (transforming factor SV40 large T antigen) protein. Gal4 is a DNA binding domain and VP16 an enhancer domain. Binding of p53 and TAg initiates expression of herpes simplex thymidine kinase that phosphorylates the radiotracer and traps it intracellularly. Intracellular trapping is demonstrated via persistent activity over the transformed murine tumour on the right. The EGFP domain can be induced to express green fluorescent protein providing fluorescent confirmation of VP16 TAg binding. Reproduced with permission [53].

 
Single photon emission computerized tomography (SPECT)
SPECT is a powerful technique that has been used to image several molecular processes at a fraction of the cost of PET. SPECT works by detecting {gamma}-emitting radionuclides via rotation of a photon detector array around the body thereby acquiring multiple projections. The {gamma} photons are detected using sodium iodide or solid-state cadmium-zinc-telluride detectors that when optimized provide a spatial resolution of 1–2 mm. Typical SPECT radionuclides include 99Tcm (6 h), 111In (2.8 days), 123I (13.2 h) and 125I (59.5 days). SPECT has commonly been used to track molecules and cells including the radiolabelling of annexin-V as an early marker of apoptosis [54].

Optical imaging
Optical methodologies are having a substantial impact on MI [55]. Compared with the hardware requirements of other imaging methodologies it is cheap, has a spatial resolution of 1–2 mm (1 µm for intravital microscopy) and possesses nanomolar sensitivity. Its principal limitation is depth penetration but recent simulations and advances suggest that several centimetres of tissue penetration will be achieved in the near future (see below).

Optical imaging technology has been enabled because of progress in mathematical modelling of tissue light propagation, the development of biocompatible near infrared probes [56, 57] and the development of sensitive photon detection technologies [58, 59]. Optical technology exploits absorption, emission, scattering and fluorescent techniques but it is fluorescence and luminescence that primarily support in vivo studies. Fluorescence is the absorption of light at one wavelength (thereby requiring a light source) and its subsequent emission at a lower wavelength. Luminescence on the other hand does not require a source of light but arises from the conversion of chemical energy to light. Generically bioluminescence (that is luminescence occurring in an organism) is typified by the luciferin/luciferase reaction where the former is the substrate and the latter the catalysing enzyme (the reaction requires ATP and O2 to progress). The male firefly Photinus pyralis exploits this reaction to emit its characteristic flashes of light. An excellent review of bioluminescence can be found at: http://www.lifesci.ucsb.edu/~biolum/.

The near infrared (NIR) is suited to in vivo imaging because the lowest coefficient of absorption (haemoglobin is the principal absorber of visible light whilst water and lipids principally absorb IR) occurs at 650–900 nm. This range of wavelengths coincides with minimal autofluorescence (this is the inherent fluorescence of tissues). The combination of photochemistry and the concept of "smart" probes have resulted in the synthesis of NIR fluorochromes and reporter probes. These substances become activated only in the presence of the desired molecular target the result of which is the amplification of emitted light. Many receptor substrates have been constructed including folate, tumour cell and protease receptor targeted probes. In the therapeutic arena "smart" NIR fluorochromes have probed and demonstrated the pharmacodynamics of matrix metalloproteinase-2 inhibition (MMP-2) as early as 8 h (Figure 7Go) following initiation of therapy [60]. The greatest challenge to optical imaging technology is its translation to opaque animals. Fluorescence molecular tomography (FMT) may provide a solution. In FMT a subject is rotated within an array of emitter/receiver charged couple devices. The recorded fluorescence, which is spatially encoded, is subsequently reconstructed tomographically. The result is a quantitative three-dimensional (3D) map with nanomolar sensitivity and spatial resolution of 1–2 mm. Numerical modelling [61] suggests that penetration of 7–14 cm in depth is achievable using appropriate fluorochromes.



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  		Figure 7. Confirmation of therapeutic inhibition of the enzyme matrix metalloproteinase-2 (MMP-2) in a murine tumour model using near infrared (NIR) imaging and a "smart" fluorescent probe. In the absence of the MMP inhibitor the NIR probe binds to its MMP target and is converted to a fluorescent substrate. The smart NIR probe will not be activated without binding to the enzyme. Reproduced with permission [60].

 
Finally, the use of fluorescent proteins and bioluminescence imaging in molecular imaging merits comment. Both approaches are prevalent in biological imaging and are commonly used to track cells including stem and tumour cells (Figure 8Go) and are commonly used as gene reporters in a wide variety of systems [62, 63]. Green fluorescent protein (GFP) (Figure 9Go) was originally extracted from the jellyfish (Figure 10Go) Aequorea victoria [64] (information on Aequorea bioluminescence can be found at: http://faculty.washington.edu/cemills/Aequorea.html). GFP suffers by having its emission wavelength (510 nm) close to the autofluorescence of many tissues. By spectrally "red-shifting" the protein via gene engineering of GFP has led to the development of red fluorescent protein (RFP). The result is that RFP can be imaged quantitatively at greater depths than GFP using the FMT technique. The advantage of bioluminescence is that there is no inherent background resulting in improved photon statistics. The technique remains limited by being semi-quantitative (it provides only a yes/no paradigm).



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  		Figure 8. Examples of bioluminescence imaging. (a) Migration of neural progenitor stem cells across the midline towards an implanted glioma in a mouse. The neural progenitor cells were labelled with the luciferin (luc) gene ex vivo so that cells expressing luciferin exhibit luminescence under appropriate conditions. (b) luc-labelled ovarian cancer cells implanted at different densities in the peritoneal cavity of a nude mouse. Note that cellular densities as low as 5 x 103 cells can be imaged. Reproduced with permission [55].

 


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  		Figure 9. Cartoon depicting the molecular structure of green fluorescent protein (GFP). GFP consists of a 11-stranded {beta}-barrel in addition to a central helix that carries the chromophore. GFP therefore acts as an energy acceptor for the protein aequorin efficiently transforming blue light (470 nm) emitted by aequorin, into green light (508 nm). Structure downloaded from Protein Data Bank (1EMA) http://www.rcsb.org/pdb/index.html.

 


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  		Figure 10. An example of the jellyfish Aequorea victoria from which the bioluminescent protein green fluorescent protein was originally extracted. Although many examples of bioluminescence exist in nature the image does not represent bioluminescence. This jellyfish was illuminated by a light during photography. (Reproduced with permission of the author.)

 

   Translating molecular imaging to man – the MR approach
Top
 Introduction
 An approach to molecular...
 Specific examples of molecular...
 Nuclear magnetic resonance
 Translating molecular imaging to...
Conclusion
 Declared interests
 References
 
Probing tumour vascularity
Imaging is increasingly called upon to study molecular based phenomena in man. Considerable advances have been made with MRI and spectroscopy. In particular functional MRI has advanced in permeability (capillary leakiness), perfusion and diffusion weighted imaging [65–68]. Permeability (or more strictly capillary leakiness) and perfusion are determined by the analysis of dynamically acquired paramagnetic contrast agent data (i.e. Gd-DTPA, gadolinium diethylenetriamine pentaacetic acid). The data are analysed by fitting the MR output to kinetic models [69]. Several kinetic models are available and consensus on their use is gradually becoming established [70]. The relationship of these techniques to the underlying biology however, remains to be validated [69]. Essentially, T1 data are recorded using a "fast" sequence, usually a gradient-echo at repeated (seconds) intervals over a pre-determined time (5–7 min). As a result of the administration of the contrast agent the T1 in the region of interest will be modulated and recorded over the time course of the study. With appropriate processing a serial set of T1 maps are created to which a given model is fit. The result is a pixel-by-pixel map of the contrast agent concentration. Other model parameters include capillary leakiness (Ktrans) and extracellular volume (ve). The perfusion estimates depend on recording the susceptibility (T2*) effect of a paramagnetic contrast agent on its first pass though a designated region of interest. The resultant drop in signal below noise is then related to the blood volume in that region. In locally advanced rectal cancers permeability determined pre-operatively was associated with response to chemotherapy [71].

Application in clinical trials
Pathological vascularity and angiogenesis [72] are the target for many new therapeutics [73, 74]. In cancer several antivascular and antiangiogenic compounds have recently completed phase I (pharmacokinetic and pharmacodynamic assay) trials. Concurrent MR studies demonstrated drug related vascular effects supporting MR data as a potential pharmacodynamic end-point [75]. There is no doubt similar studies will feature strongly in future drug trials.

Diffusion weighted imaging and combined functional imaging of tumours
Diffusion describes the random motion of molecules down a concentration gradient and is the process by which small molecular weight compounds such as Gd-DTPA access the extracellular space of tumours and other permeable tissues. MR can quantitatively describe this process such that each pixel in an image can be assigned a numerical value of diffusion. Consider a glass of water at constant pressure and temperature, the water returns a unique value of diffusion termed the diffusion constant (mm2 s–1). A glass of water though has only one compartment but in vivo a tissue will consist of several compartments including the cellular and extracellular space. Each of these presents a unique diffusion value and therefore in vivo diffusion arises from several compartments. It is therefore appropriate to term the phrase "apparent diffusion coefficient" (ADC). Another approach to thinking about ADC is as a measure of cellularity. One extreme, necrosis, presents a minimal barrier to the motion of water molecules. Highly cellular environments on the other hand are considerably more restrictive to the translational motion of water molecules. On this basis ADC in locally advanced rectal tumours was found to be strongly correlated with response to chemotherapy and chemoradiation [76]. Based on pre-clinical results it is likely that diffusion weighted imaging (DWI) is a surrogate marker of necrosis [77, 78]. Technical issues related to DWI include the sequence parameters, most notably the b-value (s mm–2). This is a measure of the degree of diffusion weighting and it is possible therefore to weight preferentially for one compartment (i.e. the extracellular rather than the cellular) over another. In pre-clinical systems DWI has convincingly demonstrated the early assessment of treatment response prior to conventional morphological change [78–82]. There is therefore considerable precedent in translating this technology into man. This diffusion technology combined with the vascular scanning mentioned above have now the capability of delivering "multifunctional" scans in a time acceptable to patients (Figure 11Go).



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  		Figure 11. Representative images from a multifunctional study of a patient with a locally advanced rectal carcinoma (outlined by the yellow arrows). (a) Axial T2 section through the section of the tumour at mid-rectal level. The soft tissue mass superior to the tumour is a recently gravid uterus. (b) The parametric permeability (capillary leakiness) map of the same tumour. Each pixel in the tumour is colour coded according to the amount of permeability (white–high, blue–low). (c) The perfusion map. High signal intensity pixels correspond to a high relative perfusion. The data indicate a poorly perfused tumour. Note the high perfusion of the recently gravid uterus. (d) The apparent diffusion coefficient map. Areas of high signal intensity indicate restricted diffusion. These functional data were acquired during the same scanning session in under 1 h.

 
Magnetic resonance spectroscopy
The MR phenomenon is based on nuclei possessing a nuclear magnetic moment, without which a MR signal cannot be generated. However, if a nucleus only resonated at one frequency it would be impossible to distinguish one molecule from another and MR would not be the powerful analytical technique it is. Unique resonances arise via the variable magnetic shielding consequent on the interaction between the magnetic field generated by the molecular electron clouds and the main magnetic field B0. In some cases a nucleus will be preferentially shielded whilst in another chemical configuration it will be less so. The result is that chemical structures posses unique spectroscopic signatures. Although the technique is limited in sensitivity particularly at clinical field strengths it does allow the non-invasive interrogation of tissue biology and/or drug metabolism in man [83]. The application particularly of 19F-MRS (where the recorded MR signal is from the 19F nucleus) has been used to follow anticancer [84, 85], antibiotic [86] and anaesthetic [87, 88] metabolism. Furthermore 19F-MRS been used to predict response of treatment to 5-fluorouracil (5FU) [89] and has demonstrated the biliary excretion of 5FU catabolites in man [90]. MRS remains a powerful analytical tool that given recent advances in MR hardware and an increase in clinical B0 systems is likely to further assess tumour and drug metabolism.


   Conclusion
Top
 Introduction
 An approach to molecular...
 Specific examples of molecular...
 Nuclear magnetic resonance
 Translating molecular imaging to...
 Conclusion
Declared interests
 References
 
MI is an established technique for the imaging of biological events in vitro. By combining molecular biology, chemistry and imaging hardware the field is beginning to have a significant impact on pre-clinical in vivo studies. With the advent of molecular medicine and therapeutics the next goal must be the translation of this technology into human studies.


   Declared interests
Top
 Introduction
 An approach to molecular...
 Specific examples of molecular...
 Nuclear magnetic resonance
 Translating molecular imaging to...
 Conclusion
 Declared interests
References
 
Dr Dzik-Jurasz is an Honorary Senior Lecturer at the Institute of Cancer Research and Honorary Consultant Radiologist at the Royal Marsden NHS Trust and the Hammersmith Hospital, London.


   References
Top
 Introduction
 An approach to molecular...
 Specific examples of molecular...
 Nuclear magnetic resonance
 Translating molecular imaging to...
 Conclusion
 Declared interests
 References
 

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