OBTAIN MORE INFORMATION FROM YOUR TARGET. in vivo Imaging Agents

Transcription

1 in vivo Imaging Agents OBTAIN MORE INFORMATION FROM YOUR TARGET

2 2 TARGETED TO YOUR APPLICATION AND VALIDATED FOR YOUR CONFIDENCE

3 Built around your applications choose the one that s right for you Acute Inflammation Angiogenesis Apoptosis Arthritis Atherosclerosis Bone Loss Cardiovascular Disease Hypertension Infectious Disease Oncology Pulmonary Vascular Disease Activatable fluorescence agents enable specific imaging of biological processes that underlie disease Cat B 680 and 750 FAST Cat K 680 FAST MMPSense 680, 750 FAST, and 645 FAST Neutrophil Elastase 680 FAST ProSense 680, 750 EX, and 750 FAST ReninSense 680 FAST Targeted fluorescence agents enable specific areas of interest to be detected, monitored and measured in vivo 2-DG 750 probe Annexin-Vivo 750 BacteriSense 645 Bacterial Detection Probe 750 COX-2 probe FolateRSense 680 IntegriSense 680, 750 and 645 HypoxiSense 680 Inflammation Probe OsteoSense 680 EX, 750 EX and 800 TLectinSense 680 Vascular fluorescence agents are distributed passively through blood vessels to enable imaging of vascularity, blood pooling near tumors and inflammation, and vascular leakage AngioSense 680 EX and 750 EX AngioSPARK 680 and 750 Superhance 680 Optical Reporter Oncology Cell Lines and Microorganisms Bioware Ultra Cell Lines Bioware Microorganisms 3

4 MORE INSIGHTFUL RESEARCH RESULTS PerkinElmer s comprehensive suite of fluorescent in vivo imaging agents enables unmatched imaging of a broad range of disease-related biomarkers and pathways in your research models. Our fluorescent agents and labels are optimized for use in the full range of PerkinElmer optical in vivo imaging systems, as well as other fluorescence microscopy systems and many in vitro and cellbased systems. FLUORESCENT IN VIVO IMAGING AGENTS Activatable Fluorescent Agents ProSense Fast: 4T1 orthotopic breast cancer model. Left: Reflectance, Right: Tomography Activatable agents are optically silent upon injection but are activated in vivo through cleavage by specific protease biomarkers of disease. Benefits include biologically specific readouts and high signal-to-noise at the target biology. The FAST platform represents the next generation of agents from PerkinElmer. Utilizing a novel small molecule design, the FAST agents offer improved specificity, accelerated activation profile and earlier imaging timepoints. Cat B 680 FAST Selective imaging of cathepsin B proteinases (Cat B). Optically silent in the unactivated state, NEV11112 becoming highly fluorescent when activated. Cat B 750 FAST NEV11098 Cat K 680 FAST Imaging of cathepsin K activity in oncology applications involving metastasis to the bone as well as a broad NEV11000 range of bone applications including bone loss, tumor-induced osteolysis and bone changes following arthritis. MMPSense 645 FAST MMPSense 680 MMPSense 750 FAST NEV10100 NEV10126 NEV10168 Neutrophil Elastase 680 FAST Fluorescent neutrophil elastase-activatable agent that is optically silent upon injection and produces NEV11169 fluorescent signal after cleavage by elastase produced by neutrophil cells. ProSense 680 ProSense 750 EX Imaging of MMP (metalloproteinase) activity is involved in many disease-related phenomena including cancer propagation, invasion and metastasis, rheumatoid arthritis and areas of cardiovascular disease. Versatile imaging of changes in cathepsin-based protease activity as seen in a number of pathological states and disease-related events including rheumatoid arthritis, cancer, atherosclerosis, angiogenesis and cardiovascular disease. NEV10003 NEV10001EX ProSense 750 FAST FAST version of ProSense, with faster kinetics and a broader imaging window. NEV11171 ReninSense 680 FAST Imaging of renin-angiotensin pathway associated with hypertension, kidney and cardiovascular disease. NEV11079 Target protease Fluorescent dyes quenched by proximity Dye fluoresces Dye fluoresces VivoTag VivoTag VivoTag VivoTag Linker Protease-specific peptide Linker Linker Peptide cleaved by protease Linker ProSense FAST Activatable Agent mechanism of action. 4

5 Small molecule labeled with fluorescent VivoTag VivoTag Binds to membrane-bound receptor IntegriSense Targeted Agent mechanism of action. IntegriSense Inflammation: Atherosclerosis (ApoE-/- mice) Targeted Fluorescent Agents Optimized in vivo imaging agents that actively target and bind to specific biomarkers. Benefits include the agents highly specific targeting to key biologies. Annexin-Vivo 750 In vivo targeting of membrane-bound phosphatidylserine exposed during the early stages of apoptosis. NEV11053 BacteriSense 645 Fast-clearing, targeted probe which binds to negatively charged lipids on the bacterial cell membrane, NEV10080 enabling the monitoring of infection progression in real time. FolateRSense 680 Highly specific and sensitive in detection of Folate Receptor protein. Can be used to closely monitor and NEV10040 quantitate tumor growth and metabolism. HypoxiSense 680 Detects the tumor cell surface expression of carbonic anhydrase 9 (CA IX) protein, which increases in NEV11070 hypoxic regions within many tumors. IntegriSense 645 Targets integrin αvβ3 expressed in oncology, atherosclerosis and angiogenesis disease models. NEV10640 IntegriSense 680 IntegriSense 750 OsteoSense 680 EX OsteoSense 750 EX OsteoSense 800 Small molecule fluorochrome to label a target ligand. Optimized for high-density loading. Optimized imaging of bone turnover through binding of hydroxyapatite. NEV10645 NEV10873 NEV10020EX NEV10053EX NEV11105 TLectinSense 680 NIR-labeled Tomato Lectin protein which has high binding affinity for glycoprotein N-acetylglucosamines on the NEV10060 surface of vascular endothelial cells. Use for vascular mapping in vivo. XenoLight RediJect COX-2 Probe Explorer kit (5 injections) Imaging probe that specifically detects the cyclooxygenase-2 (COX-2) XenoLight RediJect COX-2 Probe Standard kit (20 injections) XenoLight RediJect Non reactive control dye for COX-2 probe COX-2 Probe Control dye (5 injections) XenoLight RediJect Bacterial Detection Probe 750 (5 injections) NIR targeted probe for non-invasive detection of bacterial infections in vivo XenoLight RediJect Bacterial Detection Probe 750 (20 injections) XenoLight RediJect Non reactive control dye for RediJect Bacterial Detection Probe Bacterial Detection Probe Control dye (5 injections) XenoLight RediJect DG 750 Probe Explorer kit (5 injections) NIR targeted probe for non-invasive imaging of glucose uptake in vivo XenoLight RediJect DG 750 Probe Standard kit (20 injections) XenoLight RediJect Non-reactive control dye for RediJect 2-DG 750 probe DG 750 control dye (5 injections) 5

6 Vascular Fluorescent Agents PerkinElmer s vascular and physiologic agents are a range of highly fluorescent in vivo imaging molecules that remain highly stable and localized in the anatomy for various periods of time to enable imaging of disease physiology, vasculature, vascular permeability and angiogenesis. AngioSense 680 EX AngioSense 750 EX AngioSPARK 680 AngioSPARK 750 NEV10054EX NEV10011EX NEV10149 NEV10150 GastroSense 750 Imaging to monitor gastric emptying and the impact of various drugs on gastric motility; may also NEV11121 be used as an anatomical marker for the stomach. Genhance 680 (1 mg) Genhance 680 (5 mg) Genhance 750 (1 mg) Genhance 750 (5 mg) Imaging of vascularity, perfusion and vascular permeability. Remains localized in vasculature for 0-4 h; accumulates in tumors and arthritic joints at 24 h. Imaging of vascularity, perfusion and vascular permeability; long pharmacokinetic profile. Small molecule fluorescence agent. Use as a control or in vascular permeability imaging. NEV10117 NEV10130 NEV10118 NEV10177 Superhance 680 Imaging of vascularity, perfusion and vascular permeability; short pharmacokinetic profile. NEV10116 Multimodal Detection with Optical and microct Imaging Reveals the Context of Disease Using microct in conjunction with optical imaging provides synchronization of functional and anatomical data simultaneously and co-registered for true quantitative 3D image data. The combination of functional and anatomical imaging enables a clearer context and understanding of the mechanisms of disease. PerkinElmer IVIS Spectrum CT and Quantum FX enable the co-registration of microct and optical image data for fully multimodal in vivo imaging. Female Nu/Nu mice were intracardiacally injected with 1x10 6 MDA- MB-231-luc-D3H2Ln tumor cells. Bone metastasis by MDA-MB-231 cells was followed by bioluminescence, fluorescence (RediJect 2-DG 750 probe) with IVIS Spectrum. microct image showing metastatic lesions within the bone architecture and osteolysis was imaged with Quantum FX microct imaging system. Nu/Nu mice were implanted by intrathoracic injection of 1x10 6 NCI- H460-luc2 lung tumor cells suspended in Matrigel. Bioluminescence image shows lung tumor growth while the image on the right shows microct co-registration of the bioluminescent signal using the IVIS Spectrum CT imaging system. With IVIS Spectrum CT, you can use microct imaging with two mice simultaneously. 6

7 Fluorescent Labels and Dyes PerkinElmer fluorochromes and nanoparticles are designed specifically to enable customized development of novel superbright fluorescent imaging agents, with properties that are ideal for use in in vivo or in vitro imaging. AminoSPARK 680 (3 mg) AminoSPARK 750 (3 mg) VivoTag-S 680 (1 mg) VivoTag-S 680 (5 mg) VivoTag-S 750 (1 mg) VivoTag-S 750 (5 mg) VivoTag-S 750-MAL (1 mg) VivoTag-S 750-MAL (5 mg) VivoTag 645 (1 mg) VivoTag 645 (5 mg) VivoTag 645-MAL (1 mg) VivoTag 645-MAL (5 mg) VivoTag 680 XL-MAL (1mg) VivoTag 680 XL-MAL (5mg) VivoTag 680 XL (1 mg) VivoTag 680 XL (5 mg) Nanoparticle fluorescent label for a target ligand. Superbright with extended pharmacokenetic profile and the ability for multivalent ligand coupling. Small molecule fluorochrome to label a target ligand. Optimized for single molecule loading. Amine-reactive for labeling via an NHS ester linkage. Small molecule fluorochrome to label a target ligand. Optimized for single molecule loading. Amine-reactive for coupling via maleimide chemistry to label free cysteines or thiol groups. Amine-reactive near infrared fluorochrome for labeling via an NHS ester linkage to peptides, small molecules, proteins, antibodies or macromolecules. optimized for in vitro-in vivo imaging. Red fluorochrome for coupling via maleimide chemistry to label free cysteines or thiol groups; optimized for in vitro-in vivo imaging. NIR fluorochrome for coupling via maleimide chemistry to label free cysteines or thiol groups. Lower quenching than VivoTag-S 680. Fluorochrome for labeling small molecules, proteins, antibodies, nanoparticles or other macromolecules. Hydrolytically stable. Low self-quenching for higher loading. NEV10142 NEV10143 NEV10121 NEV10122 NEV10123 NEV10124 NEV11223 NEV11224 NEV11173 NEV11174 NEV11273 NEV11274 NEV11219 NEV11220 NEV11119 NEV11120 VivoTag 800 (1 mg) Small molecule fluorochrome to label a target ligand. Optimized for high-density loading. NEV11107 VivoTag 800 (5 mg) Small molecule fluorochrome to label a target ligand. Optimized for high-density loading. NEV11108 XenoLight CF 680 Fluorescent Labeling Kit (3 labelings) XenoLight CF 750 Fluorescent Label any peptide protein or with easy to use Kit. NIR wavelength for in vivo imaging Labeling Kit (3 labelings) XenoLight CF 770 Fluorescent Labeling Kit (3 labelings) XenoLight CF 680 NIR Fluorescent Dye (1 μmole) XenoLight CF 750 NIR Reactive fluorescent dye for bulk protein or antibody labeling Fluorescent Dye (1 μmole) XenoLight CF NIR Fluorescent Dye (1 μmole) XenoLight CF Free Acid (1 μmole) XenoLight CF Non reactive control dye for XenoLight CF dyes of same wavelength Free Acid (1 μmole) XenoLight CF Free Acid (1 μmole) XenoLight DiR (1 μmole) NIR dye for non-invasive imaging of cell homing (stem cells, T cells)

8 Employ Multimodal Detection for Deeper Understanding of Disease Models With the PerkinElmer optical in vivo imaging systems, multiple agents can be imaged and quantitated simultaneously for multiplexing analysis to evaluate a number of biomarkers or pathways relating to a biological question. In the FMT 4000, up to four different agents can be imaged in the four separate channels, allowing for a four-dimensional analysis of a particular application With the FMT 4000, up to four agents can be imaged simultaneously to allow for the quantitation of four separate biomarkers relating to a particular application. This image (left) illustrates this capability with agents imaged in the 635 nm, 670 nm, 745 nm and 785 nm channels.* *Image courtesy of Waterman, P and Nahrendorf, M, MGH/Harvard nm dye: nm dye: nm dye: nm dye: 1-1 IntegriSense ProSense Avastin Vehicle Tumor Fluorescence (pmoles) Vehicle Avastin IntegriSense Tomographic Quantification Vehicle Avastin In this sequence, IntegriSense and ProSense are imaged simultaneously to evaluate the effect of Avastin on a tumor. Representative isosurface renderings of a mouse treated with Avastin and a mouse treated with vehicle are shown. Note the differential localization of IntegriSense (blue), highlighting integrin presence, and ProSense (red), quantitating cathepsin activity within the same tumor. In addition, treatment with Avastin showed quantitative changes in integrin imaging with as little as one week of treatment. FMT Imaging Multiplexed Imaging of IntegriSense and ProSense LUMINESCENCE AGENTS XenoLight Bioluminescent/Chemiluminescent Substrates PerkinElmer offers bioluminescent substrates in a easy to use format that fit your laboratory workflow for in vivo imaging. RediJect substrates offer ultimate sensitivity and reproducibility that is critical for accurate quantitation. Obtain better results by minimizing variability in formulation, minimizing freeze/thaw and controlling batch to batch variation. RediJect D-Luciferin Ultra is a firefly Luciferase substrate, pre-formulated with a fluorescent marker, to validate your substrate injection. GL261-luc2: Monitor brain tumor growth non-invasively in vivo XenoLight RediJect Pre-formulated batch controlled D-Luciferin (K+ salt) ready for in vivo use D-Luciferin (50 injections) XenoLight RediJect Pre-formulated batch controlled D-Luciferin (K+ salt) for in vivo use D-Luciferin Ultra (50 injections) Includes a fluorescent marker to validate substrate injection XenoLight RediJect Pre-formulated batch controlled Coelenterazine h for in vivo use Coelenterazine h (50 injections) XenoLight RediJect Inflammation Pre-formulated chemiluminescent probe for monitoring inflammation Probe, Explorer kit (5 injections) XenoLight RediJect Inflammation Pre-formulated chemiluminescent probe for monitoring inflammation Probe, Standard kit (20 injections) XenoLight D-Luciferin Bioluminescence substrate for in vivo imaging with Firefly Luciferase, in bulk (K+ Salt) (1-50g) 8

9 BIOWARE BIOLUMINESCENT ONCOLOGY CELL LINES In most oncology models, brighter cell lines lead to better results. PerkinElmer offers bioluminescent cell lines covering a range of cancer models, including breast, colorectal, lung and prostate as well as lymphoma. Bioware Ultra cell lines, created using the luc2 vector, produce intensified light allowing for more sensitive non-invasive detection of cells in vivo. Some of the cell lines are bright enough to detect a single cell in vivo. With these bright cell lines your optical in vivo imaging system can start collecting tumor progression data right after injection. Bioware Ultra Oncology cell lines labeled with enhanced luc2 (pgl4) vector MDA-MB-231-luc2 - Breast Cancer metastasis to Lymph nodes post orthotopic implantation of cells HT1080-luc2 Human Fibrosarcoma Cancer Cell line T1-luc2 Murine Breast Cancer Cell line, single cell detection in vivo MDA-MB-231-luc2 Human Breast Cancer Cell line, ideal for experimental metastasis model GL261-luc2 Murine Glioma Cell line, extremely bright like 4T1-luc HepG2-luc2 Human Hepatic Cancer cell line PC-3M-luc2 Human Prostate Cancer Cell line, orthotopic, intracardiac tumor models PC-3-luc2 Human Prostate Cancer Cell line LnCaP-luc2 Human Prostate Cancer Cell line, 15 fold brighter than luc version B16-F10-luc2 Murine Melanoma Cancer Cell line, 40 fold brighter than luc version HCT-116-luc2 Human Colorectal Cancer Cell line, subcutaneous tumor models HT-29-luc2 Human Colorectal Cancer Cell line, ideal for s.c. models with metastasis Colo205-luc2 Human Colorectal Cancer Cell line U-87 MG-luc2 Human Brain Cancer Cell line, ideal for glioblastoma models NCI-H460-luc2 Human Lung Cancer Cell line, ideal for orthotopic lung tumor models EL4-luc2 Murine Lymphoma Cancer Cell line K-562-luc2 Human Leukemia Cell line, Orthotopic (intracerebral) tumor model MOLT-4-luc2 Human Leukemia Cell line ACHN-luc2 Human Renal Cancer Cell line BxPC3-luc2 Human Pancreatic Cancer Cell NCI-H460-luc2-3D co-registration of bioluminescent lung tumor with microct 4T1-luc2 - Tumor metastasis post intracardiac injection of cells (IVIS Lumina XR). MicroCT image (Quanutm FX) confirming bone degradation in the right tibia. 9

10 Bioware Oncology cell lines labeled with luc (pgl3) vector MDA-MB-231-luc-D3-H1 Human Breast Cancer MDA-MB-231-luc-D3-H2LN Human Breast Cancer MCF-7-luc-F5 Human Breast Cancer HeLa-luc Human Cervical Cancer HT-29-luc-D6 Human Colorectal Cancer LoVo-6-luc-1 Human Colorectal Cancer A549-luc-C8 Human Lung Cancer LL/2-luc-M38 Murine Lung Cancer B16-F10-luc-G5 Murine Melanoma PC-3M-luc-C6 Human Prostate Cancer LNCaP-luc-M6 Human Prostate Cancer SKOV3-luc-D3 Human Ovarian Cancer hvegf-luc/pc3m Oncology/Angiogenesis reporter cell line p53-re-luc/a549 Cancer/Apoptosis/Toxicology reporter cell line BIOWARE DUAL OPTICAL REPORTER CELL LINES Oncology cell lines, dual labeled with Luciferase and Red Fluorescent Protein tdtomato or Green Fluorescent Protein (GFP), let you get a better perspective on tumor growth and metastasis. You can follow tumor development with Luciferase while the fluorescent protein allows for better ex vivo analysis. Bioware Ultra Red 4T1-tdTomato Murine Breast cancer cell line labeled with RFP tdtomato T1-luc2-tdTomato Murine Breast cancer cell line dual labeled with Luciferase & tdtomato MDA-MB-231-tdTomato Human Breast cancer cell line labeled with RFP tdtomato MDA-MB-231-luc2-tdTomato Human Breast cancer cell line dual labeled with Luciferase & tdtomato Bioware Ultra Green 4T1-luc2-GFP Murine Breast cancer cell line dual labeled with Luciferase & GFP KU-7-luc2-GFP Human Bladder cancer cell line dual labeled with Luciferase & GFP MDA-MB-231-luc2-GFP Human Breast cancer cell line dual labeled with Luciferase & GFP NCI-N87-luc2-GFP Human Gastric cancer cell line dual labeled with Luciferase and GFP PC-3-luc2-GFP Human Prostate cancer cell line dual labeled with Luciferase and GFP

11 OPTICAL REPORTER MICROORGANISMS Optical in vivo imaging technology has been successfully used to non-invasively measure the spread of infection, monitor infection dynamics and determine the in vivo efficacy of antimicrobial compounds in various ID models. PerkinElmer offers various Gram positive and Gram negative bacteria labeled with bacterial Luciferase. One advantage with the bacterial Luciferase is that it negates the use of exogenous substrate like Luciferin. PerkinElmer also offers tools like plasmid vectors that allows you to successfully label any Gram positive or Gram negative bacteria of your choice. Bacterium Parental strain Catalog No. Bacterium Parental strain Catalog No. E. coli EPEC WS ETEC WS H. influenzae ATCC K. pneumoniae 93A L. monocytogenes ATCC S (Serotype 1/2a wild-type strain) P. aeruginosa ATCC PAO P. mirabilis ATCC S. aureus ATCC I6-MRSA ATCC ATCC UAMS S. dysenteriae 88A6205. Clinical isolate S. pneumoniae D39 Serotype HUS-TMBIG, Serotype 19A A66.1, Serotype EF3030, Serotype 19F , Serotype S. pneumoniae Serotype S. pneumoniae TIGR Strain Serotype S. pyogenes Strain 591, Group A, Serotype M S. typhimurium SL FDA Y. enterocolitica 91A1854 Clinical isolate WS Y. pseudotuberculosis YPIIIpYV (Type III secretion system), clinical isolate Optical Reporter Plasmid Vectors P-Xen5 Gram-positive lux transposon plasmid P-Xen13 Gram negative luxcdabe Vector Xen39: Klebsiella pneumoniae Xen10: Pneumonia by Streptococcus pneumoniae Xen44: Monitoring migration of UTI infection from the bladder to the kidney noninvasively in real time Xen5: P. aeruginosa infection on a biofilm 11

12 Results. Smarter. Faster. With a growing emphasis on translational insight, it is more important than ever to be able to examine the molecular mechanisms of disease and translate your in vitro models into in vivo results. PerkinElmer offers leading solutions and renowned expertise in assays, imaging and informatics that will help you bring it all together. Whether working in a well, cells or small animals, now you can focus on your science, gain insight sooner and succeed faster. Contact us at (U.S.), (Europe) or (China). Or contact us by at agentinfo@perkinelmer.com. Learn more at PerkinElmer in vivo imaging agents are optimized for use in our suite of optical preclinical imaging systems. PerkinElmer, Inc. 940 Winter Street Waltham, MA USA P: (800) or (+1) For a complete listing of our global offices, visit Copyright , PerkinElmer, Inc. All rights reserved. PerkinElmer is a registered trademark of PerkinElmer, Inc. All other trademarks are the property of their respective owners B_01 Printed in USA March 2012