Imaging
In vivo preclinical imaging reagents The reagents most used today by survey respon- dents in their in vivo preclinical imaging studies was bioluminescent markers/reporters, eg luciferins, proluciferins (61% using). This was fol- lowed by visible fluorphores/ reporters, eg green fluorescent proteins and PET tracers – Fluorine-18 based (both used by 41%) and then light produc- ing cell lines (39% using). The least used approach was label-free (utilising natural fluorescence of cer- tain molecules like collagen and elastin) (Figure 8).
Main limitations of optical in vivo imaging
Maximising the depth of tissue penetration was rated the main limitation associated with optical in vivo imaging (ie bioluminescent or fluorescent imaging). This was followed by natural scattering of photons by biological tissue; high background signal from surrounding tissue; and then small-ani- mal imaging/resolution does not parallel clinical equivalents. Rated least limiting was data inconsis- tencies between imagers (Figure 9).
Latest developments in preclinical in vivo imaging
The following snapshots provide details of how various vendors support work on in vivo preclini- cal imaging through provision of imaging instru- ments and associated imaging reagents, tracers, contrasting agents and probes.
Aspect Imaging (
www.aspectimaging.com) is a world leader in high-performance compact bench- top MRI imaging systems for preclinical research. Aspect’s M2™ platform and suite of products enables researchers to harness the power and quantitative insights of MRI for small animal phe- notyping and drug development but without the cost, complexity and technical burden of tradition- al MRI systems. With Aspect’s simple-to-use plat- form, researchers can derive deep insights into their biological questions quickly, easily and cost- effectively. The system that has no fringe magnetic field and because of this the M2 can be placed any- where in a working lab, including at a scientist’s benchtop. The novel underlying technology, (ie the compact high-performance permanent magnets, coils and gradients) addresses the primary obsta- cles that exist in the current MRI market. These include the high cost of purchasing, operating and maintaining high-field MRI systems, the complex- ity of operating complex research-based MRI sys- tems, and the physical limitations placed on tradi- tional MRI systems due to their active magnetic
Drug Discovery World Summer 2011 © HTStec 2011
Figure 7: How in vivo imaging impacts drug development
Monitors disease progression and therapeutic response in longitudinal studies
Ensures preclinical in vivo data is as predictive as possible of the clinical outcome
Provides additional insight, leading to better decision-making
Aids successful translation of in vitro to in vivo
Reduces animal usage and number of animal experiments
Reduces time to market (faster progress toward clinical trials)
Reduces development costs (eg saving in FTE, histology costs)
Reduces number of compounds failing in late phases (lower attrition rates)
3.58 3.67 3.71
1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 RANKED ORDER of impact, where 1 = least impact and 9 = greatest impact
5.27 5.05 4.88 4.72 6.24
Figure 8: Reagents respondents use today for their in vivo imaging studies
Bioluminescent Markers/Reporters eg Luciferins, Proluciferins
Visible Fluorphores/ Reporters eg Green Fluorescent Proteins PET Tracers – Fluorine-18 Based
Near-Infrared Reporter Fluorescent Protein MRI Contrasting Reagents – Gadolinium-Based Infrared Dyes for NIR imaging between 700 and 800nm Light producing cell lines
PET Tracers – Technetium-99m Based MRI Contrasting Reagents – Iron-Based Light producing animal models
SPECT Probes – Iodine-131 Based
Light producing micro-organisms PET Tracers – Carbon-11 Based
Label-free (utilise natural fluorescence of certain molecules like collagen and elastin)
4%
0% 10% 20% 30% 40% 50% 60% 70% % Responding
© HTStec 2011 8% 14% 12% 22% 18% 35% 31% 27% 25%
41% 41%
39% 61%
Figure 9: Main limitations associated with in vivo optical imaging
High background signal from surrounding tissue Natural scattering of photons by biological tissue Maximising the depth of tissue penetration
Small-animal imaging/resolution does not parallel clinical equivalents
Skin and tissue autofluorescence Co-registration anatomical location with
molecular signals from optical imaging Lack of standardised imaging protocols
Generating higher contrast Quality concerns
Lack of tissue- and disease-specific dyes or immunotargeting
Variations in animal-handling procedures eg positioning, anaesthesia and warming
Data inconsistent between imagers © HTStec 2011
3.02 3.05 3.07
2.93
2.79 2.82
2.70 2.63
1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 RATING scale, where, 1 = not limiting and 5 = highly limiting
3.84
3.34 3.37
3.14
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