Xerra: A new imaging modality to study biodistribution
Cryo-fluorescence tomography (CFT) is an imaging technology that combines cryoslicing, high-resolution imaging and analysis software into one molecular imaging platform. This multispectral fluorescence imaging technique is important for ADME (absorption distribution, metabolism, excretion) and drug distribution studies. pharmacokinetic, and pharmacodynamic studies.
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.
Imaging of biodistribution of drug outside the spine
Intrathecal injection of a Sprague Dawley rat with AAV9 labeled with Iodine-125 and expressing RFP, Imaged with SPECT/CT at 8 hours and CFT after 4 weeks.
The role of CFT in Biodistribution studies
Fluoro-tagged adeno-associated viruses (AAVs) are used to deliver genes to mammalian cells and express fluorescent marker proteins in animals. Specifically, CFT can be used to quantify fluorescence, and to differentiate different AAV strains, across the whole animal. This high-resolution confirmation is possible only through CFT technology.
Study Design
– Intrathecal injection of SD rat with AAV9 labeled with Iodine-125 and expressing RFP.
- - Imaged with SPECT/CT at 8 hrs.
- - Imaged with SPECT/CT at 8 hrs.CFT reveals biodistribution of drug outside the spine after 4 wks.
SPECT/CT at 8 hr
T
L
CFT (iRFP) at 4 wks
T
L
SPECT/CT/CFT
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L
Normalized Corrected Counts
8.0
0.25
Dimant H., et al. Multimodality Imaging Study to Determine AAV Biodistribution Compared to AAV Transduction in Whole Animals. GTND 2019.
Absorption, Distribution, Metabolism, Visualization
ADME
CFT provides high sensitivity, high specificity and faster processing in any 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 imaging data can be extrapolated for further characterization.
Tissue sections can also be transferred to slides for histology.
Biodistribution of intrathecal tracer in kidney
Tracer A
Tracer B
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.
