Oncology and preclinical imaging


Overview


The development of novel and safer cancer therapeutics that target specific molecular targets and broader disease-related processes remains a need. In vivo preclinical studies can help dissect complex biological processes related to cancer (such as angiogenesis and tumor metastasis), validate potential molecular targets, and assess therapeutic response in a whole animal model. Non-invasive preclinical studies enable real-time, quantitative measurements of therapeutic outcomes while reducing the number of animals used in research. PerkinElmer offers targeted, activatable, and vascular fluorescent agents, as well as bioluminescent oncology cell lines, for preclinical imaging of cancer.


Products for oncology preclinical studies


Angiogenesis

AgentAgent TypeAgent MechanismAvailable Wavelengths and optimal in vivo imaging time (post-injection)Route of metabolism/ background tissue(s)Validated imaging methods*
IntegriSense™Targeted; fluorescentBinds to α5β3 integrin. This integrin is upregulated in activated endothelial cells during angiogenesis.645 nm (6-24 h), 680 nm (3-48 h), 750 nm (24 h)Bladder/kidneys (645 nm), kidneys/intestine (680 nm), kidneys (750 nm)In vivo/ex vivo; in vitro microscopy
HypoxiSense™Targeted; fluorescentBinds to carbonic anhydrase IX which is expressed in hypoxic tissue, a result of abherrant vasculature.680 nm (24 h)KidneysIn vivo/ex vivo; flow cytometry; in vitro microscopy
TLectinSense™Targeted; fluorescentBinds to tomato lectin, a well-known tool for studying for studying tumor angiogenesis and measuring microvessel density. This agent provides direct labeling of the vascular endothelial cells.680 nm (6 h)Overall vascular backgroundIn vivo/ex vivo; flow cytometry; in vitro microscopy
AngioSense®Vascular; fluorescentA high molecular weight agent with a moderate blood half-life (7 hours), used to assess vascular leak, with ideal imaging times of 24 hours post-injection.680 nm (24 hours)
750 nm (24 hours)
Low liver lungIn vivo/ex vivo; flow cytometry; in vitro microscopy
AngioSPARK®Vascular; fluorescentPegylated fluorescent nanoparticles that remain localized in the vasculature for extended periods of time and enable imaging of blood vessels and angiogenesis680 nm (0 - 4 hours)Long term tissue accumulationIn vivo
Superhance®Vascular; fluorescentBlood pooling agent680 nm (0.5 - 24 h)BladderIn vivo

Apoptosis

AgentAgent TypeAgent MechanismAvailable Wavelengths and optimal in vivo imaging time (post-injection)Route of metabolism/ background tissue(s)Validated imaging methods*
Annexin-Vivo™Targeted; fluorescentLabels cells that are undergoing the early stages of apoptosis750 nm (2 h)Kidneys (high), liverIn vivo/Ex vivo, Flow cytometry, In vitro microscopy

Tumor growth

AgentAgent TypeAgent MechanismAvailable Wavelengths and optimal in vivo imaging time (post-injection)Route of metabolism/ background tissue(s)Validated imaging methods*
Cat B FAST™Activatable; fluorescentProduces fluorescent signal after cleavage by Cathepsin B produced by tumor cells680: 6-24 hours
750: 6-24 hours
Salivary glands, liver, kidneysIn vivo, flow cyometry, in vitro cell microscopy, frozen tissue labeling
MMPSense®Activatable; fluorescentMatrix metalloproteinase (MMP)-activatable agent that produces fluorescent signal after cleavage by disease related MMP’s. MMP activity is involved in many disease-related processes including cancer progression, invasion and metastasis.645 FAST*: 24 h (6-24 h)
680: 24 h (24-36 h)
750 FAST*: 12 h (12-24 h)
Liver, kidneys (645 FAST, 750 FAST)
Liver only (680)
In vivo
ProSense®Activatable; fluorescentActivated by key disease associated proteases such as Cathepsin B, L, S and Plasmin. Can be used as a marker for disease progression in animal tumor models680: 24 h (24-48 h)
750: 24 h
750 FAST*: 6-24 h

Liver (680)
Low liver (750)
Low liver, bladder (750 FAST)

In vivo, flow cytometry, in vitro cell microscopy
COX-2 probeTargeted; fluorescentEfficiently target cyclooxygenase-2 (COX-2), which is normally absent from cells, but is found at high levels in inflammatory lesions and in many premalignant and malignant tumors600: 3 hKidney and liverIn vivo, in vitro cell microscopy
FolateRSense™Targeted; fluorescentHighly specific and sensitive in its detection of Folate Receptor alpha (FRA); can be used to closely monitor and quantitate tumor growth and metabolism680: 6 h (6-24 h)kidneysIn vivo, flow cytometry, in vitro cell microscopy, frozen tissue labeling
IntegriSense™Targeted; fluorescentSmall molecule αvß3 integrin antagonist that contains a NIR fluorophore reporter. This targeted agent detects increased integrin expression associated with neovasculature, tumors, and some inflammatory cells associated with atherosclerosis.645 nm (48 h)
680 nm (24 h)
750 nm (24 h)
Bladder/kidneys (645 nm)
Kidneys/intestine (680 nm)
Kidneys (750 nm)
In vivo/Ex vivo, Flow cytometry, In vitro microscopy
Transferrin-Vivo™Targeted; fluorescentRecombinant transferrin conjugated to VivoTag dye; designed to bind to transferrin receptors expressed in cancer cells.770: 24 hLiver, kidneyIn vivo, ex vivo, flow cytometry, in vitro cell microscopy, frozen tissue labeling
FolateRSense™Targeted; fluorescentHighly specific and sensitive in its detection of Folate Receptor alpha (FRA); can be used to closely monitor and quantitate tumor growth and metabolism680: 6 h (6-24 h)kidneysIn vivo, flow cytometry, in vitro cell microscopy, frozen tissue labeling
OsteoSense®Targeted; fluorescentBisphosphonate imaging agent that enables imaging of bone growth and resorption; can be used to measure bone cancer metastasis.680: 3-24 h
750: 3-24 h
800: 3-24 h
BladderIn vivo
TLectinSense™Targeted; fluorescentTargets the vasculature and enables imaging of tumor neo-vasculature, characterized by the development of abnormal, leaky and tortuous blood vessels.680 nm (6 h)Overall vascular backgroundIn vivo/ex vivo; flow cytometry; in vitro microscopy
AngioSense®Vascular; fluorescentA high molecular weight agent with a moderate blood half-life (7 hours), used to assess vascular leak, with ideal imaging times of 24 hours post-injection.680 nm (24 hours)
750 nm (24 hours)
Low liver lungIn vivo/ex vivo; flow cytometry; in vitro microscopy
AngioSPARK®Vascular; fluorescentPegylated fluorescent nanoparticles that remain localized in the vasculature for extended periods of time and enable imaging of blood vessels and angiogenesis680 nm (0 - 4 hours)Long term tissue accumulationIn vivo
Superhance®Vascular; fluorescentBlood pooling agent680 nm (0.5 - 24 hours)BladderIn vivo
Bioware Ultra Cell LinesBioluminescence or dual bioluminescence/ fluorescenceBioluminescent oncology cell lines (also known as Bioware cell lines) are stably transfected with a luciferase (luc or luc2) reporter gene that allows you to visualize the growth of the cells in vivo. The cell lines are injected into an appropriate mouse model to monitor early tumor development, monitor tumor growth and metastases, quantify tumor burden in a whole animal model, and follow therapeutic responses non-invasively.n/aIn vivo, ex vivo (dual)

Metastasis

AgentAgent TypeAgent MechanismAvailable Wavelengths and optimal in vivo imaging time (post-injection)Route of metabolism/ background tissue(s)Validated imaging methods*
2-DG 750 ProbeTargeted; fluorescentIn vivo targeting of tumors that typically exhibit elevated glucose uptake rate in comparison to surrounding tissues820: 3 h
BladderIn vivo
MMPSenseActivatable; fluorescentMatrix metalloproteinase (MMP)-activatable agent that produces fluorescent signal after cleavage by disease related MMP’s. MMP activity is involved in many disease-related processes including cancer progression, invasion and metastasis.645 FAST*: 24 h (6-24 h)
680: 24 h (24-36 h)
750 FAST*: 12 h (12-24 h)
Liver, kidneys (645 FAST, 750 FAST)
Liver only (680)
In vivo
OsteoSenseTargeted; fluorescentBisphosphonate imaging agent that enables imaging of bone growth and resorption; can be used to measure bone cancer metastasis.680: 3-24 h
750: 3-24 h
800: 3-24 h
BladderIn vivo
Bioluminescent oncology cell linesBioluminescence or dual bioluminescence/ fluorescenceBioluminescent oncology cell lines (also known as Bioware cell lines) are stably transfected with a luciferase (luc or luc2) reporter gene that allows you to visualize the growth of the cells in vivo. The cell lines are injected into an appropriate mouse model to monitor early tumor development, monitor tumor growth and metastases, quantify tumor burden in a whole animal model, and follow therapeutic responses non-invasively.n/aIn vivo, ex vivo (dual)

Hypoxia

AgentAgent TypeAgent MechanismAvailable Wavelengths and optimal in vivo imaging time (post-injection)Route of metabolism/ background tissue(s)Validated imaging methods*
HypoxiSenseTargeted; fluorescentDetects the tumor cell surface expression of carbonic anhydrase 9 (CA IX) protein, which increases in hypoxic regions within many tumors, especially in cervical, colorectal, non-small cell lung tumors680: 24 hKidneyIn vivo, flow cytometry, in vitro cell microscopy, frozen tissue labeling

Vasculature

AgentAgent TypeAgent MechanismAvailable Wavelengths and optimal in vivo imaging time (post-injection)Route of metabolism/ background tissue(s)Validated imaging methods*
AngioSenseVascular; fluorescentA high molecular weight agent with a moderate blood half-life (7 hours), used to assess vascular leak, with ideal imaging times of 24 hours post-injection.680 nm (24 hours)
750 nm (24 hours)
Low liver lungIn vivo/ex vivo; flow cytometry; in vitro microscopy
AngioSPARKVascular; fluorescentPegylated fluorescent nanoparticles that remain localized in the vasculature for extended periods of time and enable imaging of blood vessels and angiogenesis680 nm (0 - 4 hours)Long term tissue accumulationIn vivo
Cat B FASTActivatable; fluorescent680: 6-24 hours, 750: 6-24 hoursSalivary glands, liver, kidneysIn vivo, flow cyometry, in vitro cell microscopy, frozen tissue labeling
IntegriSenseTargeted; fluorescentSmall molecule αvß3 integrin antagonist that contains a NIR fluorophore reporter. This targeted agent detects increased integrin expression associated with neovasculature, tumors, and some inflammatory cells associated with atherosclerosis.645 nm (48 h)
680 nm (24 h)
750 nm (24 h)
Bladder/kidneys (645 nm)
Kidneys/intestine (680 nm)
Kidneys (750 nm)
In vivo/Ex vivo, Flow cytometry, In vitro microscopy
Superhance®Vascular; fluorescentBlood pooling agent680 nm (0.5 - 24 h)BladderIn vivo

Choosing the right agent

When choosing an agent for acute inflammation studies, several factors should be taken into consideration:

  • Fluorescent vs. Chemiluminscent agents: Be sure to choose the proper agent for your instrumentation. Some imagers can measure both chemiluminescence and fluorescence, while others can only measure one or the other. 
  • Dye excitation/emission wavelength: Some fluorescent agents are available with excitation wavelengths that range from 645 nm to 800 nm. Be sure to pick a wavelength that is appropriate for both your instrument and application. Most microscopes filters are not suitable for wavelengths above 680 nm.  However deep tissue imaging typically has less background fluorescence and works better with longer wavelengths (750 nm- 800 nm). 
  • Agent clearance time is typically faster for activatable agents (particularly the FAST™ platform) which allows for re-injection after shorter time periods.  
  • Agent specificity: For targeted and activatable agents, it is important to remember that the protein or enzyme that the agent is targeting needs to be present and well expressed in your mouse model. 
  • In vivo distribution: Some agents might accumulate in organs at timepoints which could interfere with your study. Be sure to check the biodistribution profile of each agent of interest. 
  • Type of imaging required for your study: Vascular agents for example, while useful in assessing vascularity changes in the mouse, do not make good agents for in vitro cell imaging or tissue analysis. If these types of analyses are desired, targeted or activatable agents might be a better choice for you.


Application notes and posters


  • Poster: Non-Invasive Near-Infrared Quantitative Tomography and Agents for Quantification of Early Anti-Angiogenic Treatment Efficacy 
  • Poster: Quantifying Syngeneic Breast Cancer Metastasis to the Lung and Response to Therapy Using Fluorescence Molecular Tomography (FMT) 
  • Poster: Non-invasive FMT quantification of folate receptor expression in mouse tumor xenografts with a new near-infrared fluorescent folate agent 
  • Poster: In vivo imaging of tumor hypoxia by a new near-infrared fluorescent carbonic anhydrase IX-targeted agent 
  • Poster: In Vivo Quantification of Integrin-Targeted and Protease-Activated Imaging Agents in Response to Anti-Angiogenic Therapy using Quantitative Fluorescence Tomography


Citations


Browse or search the PerkinElmer Citations Library for oncology preclinical imaging citations.