Our diverse team of experts has experience in instrument engineering, signal processing, and pharmaceutical R&D, collectively resulting in a long history designing and executing imaging studies. Our scientists have performed hundreds of imaging studies across multiple therapeutic research areas, including oncology, neuroscience, inflammation, cardiovascular, metabolic, and musculoskeletal, and our experience runs the gamut of applications. We understand the physiological and biochemical mechanisms that affect imaging—targets, models, kinetics, and more. This vast hands-on experience allows us to understand drug behavior and translate knowledge to provide effective studies and useful data.
We define imaging as assays that enable visualization of subcellular distribution and processes all the way to translational and diagnostic clinical imaging biomarkers, including everything in between. With all imaging techniques, we use methods to ensure data is quantifiable and leverage our powerful analytics platform to ensure that results can be used to drive meaningful decisions.
Execution of these studies requires the skills of many scientific disciplines and the structure to enable the complex coordination of all facets of the experiment, including animal models, radiolabeled molecules, multiple timepoints, and multi-modal imaging. Invicro has built a research laboratory network with services that are necessary to support these imaging endpoints, and we continue to advance and add to these services to meet the needs of our sponsors. We often develop imaging protocols for novel compounds, work through the radiochemistry needs together with the sponsor, and assist with animal model development as needed. We can perform imaging studies on a range of different species with a large number of administration routes available. Species include rodent, dog, cat, pig, rabbit, sheep, and non-human primates as well as surgical and oncology models.
|Key Supporting Capabilities|
|Disease model development, including tumor inoculation|
|Pharmacology, efficacy, and biomarker study execution|
|Drug and imaging agent administration, including during scanning|
|Blood collection for whole blood, plasma, or serum PK analysis|
|Gamma and liquid scintillation counting (biodistribution studies)|
|Focal beam radiation|
Invicro is imaging modality agnostic and can apply imaging techniques across therapeutic areas and species. Studies may be single or multi-modal and may combine multiple isotopes or contrast mechanisms. When designing any study, we combine imaging theory, published methods, and the technical and professional expertise of our staff to ensure the appropriate technique is applied to best answer the biological question.
|PET||Quantitative Whole-Body Autoradiography|
|MRI/MRS||Optical 2D and 3D cryotomography|
|x-ray CT||Cryo-Fluorescence Tomography (CFT)|
|Bioluminescence||Routine and Specialized Histology|
|Ultrasound||Blood and urine analysis|
|Optoacoustic Imaging||Flow Cytometry (FACS)|
|Radioligand binding assays (cells and tissues)|
Use radiolabeled compounds to determine a treatment strategy by combining therapeutics and diagnostics in the same agent, for example with 111In and 225Ac
Antibody-Drug Conjugate (ADC) Biodistribution
Use of a dual-isotope quantitative 3D autoradiography method for simultaneous and quantitative assessment of both antibody and drug conjugate tumor distribution and kinetics. Visualize the intratumoral distribution of the two major components of an ADC, the mAb and small molecule drug conjugate simultaneously in three dimension over time.
Biodistribution of Radiolabeled Compounds
Radiolabeling of compounds such as antibodies, followed by longitudinal PET or SPECT imaging for biodistribution and dosimetry evaluation, can include sub-organ analysis via longitudinal radial profiling. See this publication for more information.
Candidate and Dose Selection Studies
Invicro can perform competitive tissue binding assays comparing labelled and non-radioactive drugs through high-resolution ex vivo imaging and in vitro validation to confirm radioligand binding and inform dose selection for subsequent studies.
Determining Target Engagement and Dose Occupancy Studies
Determine the relationship between plasma concentration and target receptor engagement. Various methods are available, such as homogenate binding assays, autoradiography, and in vivo imaging. Cell binding affinity, internalization, and bioactivity analysis can also be performed.
Determining Target Expression
Understanding the drug target is critical and Invicro has expertise in studying target expression in ex vivo clinical and pre-clinical material. Various techniques are available to confirm target expression (e.g. autoradiography, ELISA, FACS, and immunohistochemistry).
Drug Efficacy and Pharmacology
Dynamic MR Contrast Enhancement (DCE)
Dynamic contrast enhanced (DCE) T1-weighted MRI provides functional characterization of tumor perfusion and permeability, which may be heterogeneous. We have developed analysis tools for semi-automated estimation of parametric maps or ROI analysis.
High-Throughput Compound Screening
Identify compounds of interest for subsequent analysis. Develop workflows, methods, and software tools to allow efficient high-volume compound screening.
Labeling of Drugs and Biomarkers
Invicro has dedicated R&D and GMP radiochemistry teams to support preclinical and clinical development, including short-lived and long-lived isotopes used for quantitative PET or SPECT imaging. Fluorescent labelling techniques are also available.
Metabolite Analysis by MRS
Single voxel, in vivo 1H MRS is available at Invicro. This technique can be used for longitudinal monitoring and therapy response of various metabolites and processes in parallel, for example, neurochemicals (Glu/Gln and GABA) and energy metabolism (PCr, lactate, and ATP). This method is also translatable to clinic. Invicro has various pulse sequences available (PRESS, semiLASER, ISIS, and STEAM) in addition to an automated LC Model (LCModel and Provencher) analysis workflow. Other applications are tissue pH (intra- and extracellular by P-31), quantification, distribution, and metabolism of exogenous F-19 labelled compounds as well as high-resolution ex vivo MR spectroscopy of tissue extracts.
Monitoring Gene Expression
3D CFT images of an in vivo administered adeno-associated virus (AAV) vector carrying a green fluorescent protein (GFP) reporter gene in a rodent allows direct visualization of viral trafficking and gene expression. This can be applied to evaluate the effect of gene and cell therapies. Registration to white light images and fly through movie generation provides accurate localization of signal.Visualization of anatomical details with high soft tissue contrast using in vivo MRI can evaluate morphological changes in brain, tumors, and more and detect small lesions (e.g., in the lung). The spatial resolution can be tailored as needed, as in the example below, for details such as optical nerves. Invicro can employ all standard MR contrasts and has access to various RF coils for whole body or body parts, with gating for improved spatial resolution and customizable analysis. CT and ultrasound are also available for structural imaging.
Modeling to Inform Clinical Protocol Design
Combine preclinical discovery work with distributed tumor model simulations to directly guide clinical imaging protocols to support the estimation of tumor properties in human subjects and guide the design of first-in-human oncology clinical imaging protocols with novel biomarkers.
Pharmacological MR Imaging (phMRI)
Quantifying changes in BOLD (view example below for Traxoprodil and Ketamine). This allows in vivo, longitudinal assessment of non-labelled compounds. Various mathematical modelling and simulation methods are available. Brain atlases are available for various species, including rodents and non-human primates.
Invicro uses pharmacokinetic modeling to support study design and interpretation of experimental data. Invicro often provides PK modeling support in an iterative fashion to continually learn and modify the model and/or model parameters to build confidence in simulations to support experimental study design and clinical translation. The figure uses PK modeling to demonstrate the impact of molecular weight on tumor accumulation while keeping all other model parameters constant.
PK/PD Efficacy Evaluation
Screening Gene Delivery in vivo with Bioluminescence Imaging
Bioluminescence imaging (BLI) using luciferase reporters has revolutionized discovery research and is now a mainstay for in vivo testing in oncology (e.g., oncolytic virus and immune cell tracking) and for evaluating gene therapies delivered using lipid nanoparticles, viruses, and siRNA. In this example, different mRNA gene products were evaluated with or without supplemental test agents to determine effectiveness in promoting expression.
Gene delivery agent screening study: in vivo (italics in vivo) mRNA gene delivery time course for multiple test agents (route: IM) quantified by bioluminescence imaging. The graph shows hindlimb photon flux (p/s) vs. time, with the data plotted as geometric mean +/- standard error in geometric mean. Example images highlight a combination treatment benefit vs. Single agent for test Test Agent 2.
Visualization of anatomical details with high soft tissue contrast using in vivo MRI can evaluate morphological changes in brain, tumors, and more and detect small lesions (e.g., in the lung). The spatial resolution can be tailored as needed, as in the example below, for details such as optical nerves. Invicro can employ all standard MR contrasts and has access to various RF coils for whole body or body parts, with gating for improved spatial resolution and customizable analysis. CT and ultrasound are also available for structural imaging.
Diffusion-based MRI can be used to localize brain damage and monitor disease progression monitoring. Modelling for quantitative parametric maps is available.
Vascular Imaging (In Vivo and Ex Vivo with AltaBlu)
AltaBlu Prime is a proprietary radiopaque vascular casting agent used to image vasculature using microCT and 3D vasculature in whole animal and organ level angiogenesis in tumors and implants. Use in preclinical disease models such as neurodegeneration, stroke, and cancer. Obtain segmentation, calculation, and visualization of vessel and radius and density. View a deeper branch-by-branch analysis of branch radius, length, vessel branching fraction, and tortuosity with characterization of vessel properties.
We specialize in the application of imaging in drug research and have experience working in multiple therapeutic areas. Our mission is to be a scientific partner to our sponsoring companies who benefit from our services for the rapid collection of data and advancement of their programs.
Invicro’s discovery research team can provide guidance on all stages of the early drug development process from the choice of labeling technique, most appropriate imaging modality, choice of animal model, finalized study design, and preferred analysis endpoints to answer biological questions and produce meaningful results. Invicro has multiple sites globally with preclinical imaging facilities in Boston, Michigan, San Diego, New Haven, and London, UK and the site of choice will be dependent on sponsor needs.