Drug Discovery
Drug Discovery

Cryo-Fluorescence Tomography (CFT) is a powerful imaging modality for drug discovery studies. This leading-edge technology can be extremely valuable for the characterization of a drug candidate. 3D biodistribution and localization of drug candidates like small molecules, antibody drug conjugates, or diagnostic antibodies can be visualized across an entire sample and/or animal using CFT. This makes CFT a powerful screening tool for early drug candidates by helping understand drug’s pharmacodynamic data including affinity and selectivity for their targets, and stability in an animal model.

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Biodistribution

CFT – high sensitivity, high specificity, faster processing in a laboratory setting

Radiolabeled pharmaceuticals and probes are common in the drug discovery world and take time and resources to develop. CFT offers unique advantages in the discovery phase by adding a streamlined imaging modality for drug characterization utilizing fluorescent reporters. CFT can provide valuable insight into absorption, distribution, metabolism and excretion (ADME) information and visualization of a whole animal in a cost-effective time sensitive manner. In addition, specific organs can be analyzed, and further characterization can be extrapolated from a study. Tissue sections can also be transferred to slides for histology.

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3D-CFT PK analysis of rodent brain

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Delivery of antisense (ASOs) labeled with Cy7 are evaluated in mouse brains.

Time course study shows biodistribution of ASOs over time.

Biodistribution data with greater 3D resolution

In this experiment, a fluorescent tracer, Cy7 conjugated therapeutic, was injected into murine models. Their brains were collected at different time points. Using CFT, the brains were sliced, imaged and processed. 3D reconstructions showed the movement of the tracer across the brain from 1 hour to 12 hours (top panel). Tracer concentration was quantified across time and in different regions of the brains (bottom panel). Using CFT, a drug’s pharmacokinetics can be visualized, quantified and traced in real-time. 

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ADME

CFT – Brand New Workflow

Cryo-fluorescence tomography(CFT) is a brand new workflow combining cryoslicing, high-resolution imaging and software into one molecular imaging platform. This multispectral fluorescence imaging technique is useful for drug distribution studies.

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Tracer A

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Tracer B

Image of kidney in rat model.

Biodistribution of intrathecal tracer in kidney

Two tracers – simultaneously

In a study of renal blood flow, renal clearance of 2 tracers, was measured simultaneously. Tracer A was intrathecally injected first and 50 minutes later, Tracer B was administered intravenously. A white light image was also taken for anatomical context and showed the segmented vascular structure of the kidney. A slice-by-slice overlay was viewed through our powerful software. 3D renderings of renal fluorescence distribution and structural mapping showed the precise distribution of tracers.

The Next Generation of Imaging. Xerra.