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Nuklearmedizin 2016; 55(02): 63-70
DOI: 10.1055/s-0037-1616471
Review
Schattauer GmbH

Fluorescence and Cerenkov luminescence imaging

Applications in small animal researchFluoreszenz- und Cerenkov-Lumineszenz-BildgebungAnwendung in der Kleintier-Forschung
J. Schwenck
1   Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany
1   Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany
,
K. Fuchs
1   Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany
,
S. H. L. Eilenberger
1   Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany
,
A.-M. Rolle
1   Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany
,
S. Castaneda Vega
1   Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany
,
W. M. Thaiss
1   Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany
1   Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany
,
F. C. Maier
1   Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University Tübingen, Germany
› Author Affiliations
Further Information

Publication History

received: 17 December 2015

accepted: 21 December 2015

Publication Date:
09 January 2018 (online)

Also available at
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Summary

This review addresses small animal optical imaging (OI) applications in diverse fields of basic research. In the past, OI has proven to be cost- and time-effective, allows real-time imaging as well as high-throughput analysis and does not imply the usage of ionizing radiation (with the exception of Cerenkov imaging applications). Therefore, this technique is widely spread – not only geographically, but also among very different fields of basic research – and is represented by a large body of publications. Originally used in oncology research, OI is nowadays emerging in further areas like inflammation and infectious disease as well as neurology. Besides fluorescent probe-based contrast, the feasibility of Cerenkov luminescence imaging (CLI) has been recently shown in small animals and thus represents a new route for future applications.

Thus, this review will focus on examples for OI applications in inflammation, infectious disease, cell tracking as well as neurology, and provides an overview over CLI.

Zusammenfassung

Diese Übersicht befasst sich mit verschiedenen Anwendungsgebieten der optischen Bildgebung im Bereich der Grundlagenforschung an Kleintieren. Die optische Bildgebung hat sich als eine kosten- und zeitgünstige Alternative zu anderen bildgebenden Modalitäten erwiesen, sie ermöglicht das Verfolgen von biologischen Prozessen in vivo in Echtzeit sowie Hochdurchsatzanalysen und impliziert nicht notwendigerweise die Verwendung ionisierender Strahlung – mit Ausnahme der Cerenkov-Lumineszenz-Bildgebung. Weiterhin ist die optische Bildgebung geografisch und in verschiedensten Fachrichtungen in der Anwendung sehr weit verbreitet. Ursprünglich vor allem in der onkologischen Grundlagenforschung eingesetzt, findet die optische Bildgebung mittlerweile auch in anderen Forschungsgebieten wie beispielsweise bei entzündlichen, infektiösen oder neurologischen Krankheiten Anwendung. Neben der Fluoreszenz-Bildgebung wird neuerdings die Cerenkov-Lumineszenz als neues Kontrastierungsverfahren in der Kleintierforschung verwendet.

Keywords

Optical imaging - small animal - fluorescence - Cerenkov luminescence

Schlüsselwörter

Optische Bildgebung - Kleintier - Fluoreszenz - Cerenkov-Lumineszenz
 

  • References

  • 1 Abulrob A, Brunette E, Slinn J. et al. Dynamic analysis of the blood-brain barrier disruption in experimental stroke using time domain in vivo fluorescence imaging. Mol Imaging 2008; 7: 248-262.
    PubMedGoogle Scholar
  • 2 Balkin ER, Kenoyer A, Orozco JJ. et al. In vivo localization of 90Y and 177Lu radioimmunoconjugates using Cerenkov luminescence imaging in a disseminated murine leukemia model. Cancer Res 2014; 74: 5846-5854.
    CrossrefPubMedGoogle Scholar
  • 3 Bremer C, Tung CH, Weissleder R. In vivo molecular target assessment of matrix metalloproteinase inhibition. Nat Med 2001; 7: 743-748.
    CrossrefPubMedGoogle Scholar
  • 4 Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 1994; 264: 569-571.
    CrossrefPubMedGoogle Scholar
  • 5 Carpenter CM, Ma X, Liu H. et al. Cerenkov luminescence endoscopy: improved molecular sensitivity with beta-emitting radiotracers. J Nucl Med 2014; 55: 1905-1909.
    CrossrefPubMedGoogle Scholar
  • 6 Cheng Z, Wu Y, Xiong Z. et al. Near-infrared fluorescent RGD peptides for optical imaging of integrin alphavbeta3 expression in living mice. Bioconjug Chem 2005; 16: 1433-1441.
    CrossrefPubMedGoogle Scholar
  • 7 Cherenkov PA. Radiation from high-speed particles. Science 1960; 131: 136-142.
    CrossrefPubMedGoogle Scholar
  • 8 Ciarrocchi E, Belcari N, Guerra AD. et al. Cherenkov luminescence measurements with digital silicon photomultipliers: a feasibility study. EJNMMI Phys 2015; 2: 32.
    CrossrefPubMedGoogle Scholar
  • 9 Cortez-Retamozo V, Swirski FK, Waterman P. et al. Real-time assessment of inflammation and treatment response in a mouse model of allergic airway inflammation. J Clin Invest 2008; 118: 4058-4066.
    CrossrefPubMedGoogle Scholar
  • 10 Costa C, Incio J, Soares R. Angiogenesis and chronic inflammation: cause or consequence?. Angiogenesis 2007; 10: 149-166.
    CrossrefPubMedGoogle Scholar
  • 11 Curtis A, Calabro K, Galarneau JR. et al. Temporal variations of skin pigmentation in C57BL/6 mice affect optical bioluminescence quantitation. Mol Imaging Biol 2011; 13: 1114-1123.
    CrossrefPubMedGoogle Scholar
  • 12 Dothager RS, Goiffon RJ, Jackson E. et al. Cerenkov radiation energy transfer imaging: a novel method for optical imaging of PET isotopes in biological systems. PLoS One 2010; 5: e13300.
    CrossrefPubMedGoogle Scholar
  • 13 Feldmann M, Brennan FM, Maini RN. Rheumatoid arthritis. Cell 1996; 85: 307-310.
    CrossrefPubMedGoogle Scholar
  • 14 Firestein GS, Paine MM. Stromelysin and tissue inhibitor of metalloproteinases gene expression in rheumatoid arthritis synovium. Am J Pathol 1992; 140: 1309-1314.
    PubMedGoogle Scholar
  • 15 Freise AC, Wu AM. In vivo imaging with antibodies and engineered fragments. Mol Immunol 2015; 67: 142-152.
    CrossrefPubMedGoogle Scholar
  • 16 Fuchs K. Molecular mechanisms of regulation in experimental arthritis 2012 ((AUTOR BITTE PRÜFEN))
    PubMed
  • 17 Hasenberg A, Hasenberg M, Männ L. et al. Catchup: a mouse model for imaging-based tracking and modulation of neutrophil granulocytes. Nat Methods 2015; 12: 445-452.
    CrossrefPubMedGoogle Scholar
  • 18 Hintersteiner M, Enz A, Frey P. et al. In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe. Nat biotechnol 2005; 23: 577-583.
    CrossrefPubMedGoogle Scholar
  • 19 Hu H, Cao X, Kang F. et al. Feasibility study of novel endoscopic Cerenkov luminescence imaging system in detecting and quantifying gastrointestinal disease: first human results. Eur Radiol 2015; 25: 1814-1822.
    CrossrefPubMedGoogle Scholar
  • 20 Jaiswal JK, Mattoussi H, Mauro JM. et al. Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat Biotechnol 2002; 21: 47-51.
    PubMedGoogle Scholar
  • 21 King MT, Carpenter CM, Sun C. et al. Beta-radioluminescence imaging: A comparative evaluation with Cerenkov luminescence imaging. J Nucl Med 2015; 56: 1458-1464.
    CrossrefPubMedGoogle Scholar
  • 22 Kirchherr AK, Briel A, Mader K. Stabilization of indocyanine green by encapsulation within micellar systems. Mol Pharm 2009; 6: 480-491.
    CrossrefPubMedGoogle Scholar
  • 23 Klingstedt T, Nilsson KP. Luminescent conjugated poly- and oligo-thiophenes: optical ligands for spectral assignment of a plethora of protein aggregates. Biochem Soc Trans 2012; 40: 704-710.
    CrossrefPubMedGoogle Scholar
  • 24 Klohs J, Grafe M, Graf K. et al. In vivo imaging of the inflammatory receptor CD40 after cerebral ischemia using a fluorescent antibody. Stroke 2008; 39: 2845-2852.
    CrossrefPubMedGoogle Scholar
  • 25 Klunk WE, Engler H, Nordberg A. et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 2004; 55: 306-319.
    CrossrefPubMedGoogle Scholar
  • 26 Kothapalli SR, Liu H, Liao JC. et al. Endoscopic imaging of Cerenkov luminescence. Biomed Opt Express 2012; 3: 1215-1225.
    CrossrefPubMedGoogle Scholar
  • 27 Lee CM, Jang D, Cheong SJ. et al. Optical imaging of MMP expression and cancer progression in an inflammation-induced colon cancer model. Int J Cancer 2012; 131: 1846-1853.
    CrossrefPubMedGoogle Scholar
  • 28 Lee HW, Jeon YH, Hwang M-H. et al. Dual reporter gene imaging for tracking macrophage migration using the human sodium iodide symporter and an enhanced firefly luciferase in a murine inflammation model. Mol Imaging Biol 2013; 15: 703-712.
    CrossrefPubMedGoogle Scholar
  • 29 Lee HW, Yoon SY, Singh TD. et al. Tracking of dendritic cell migration into lymph nodes using molecular imaging with sodium iodide symporter and enhanced firefly luciferase genes. Sci Rep 2015; 5: 9865.
    CrossrefPubMedGoogle Scholar
  • 30 Lin AJ, Liu G, Castello NA. et al. Optical imaging in an Alzheimer’s mouse model reveals amyloid-dependent vascular impairment. Neurophotonics 2014; 1: 011005.
    CrossrefPubMedGoogle Scholar
  • 31 Liu H, Carpenter CM, Jiang H. et al. Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study. J Nucl Med 2012; 53: 1579-1584.
    CrossrefPubMedGoogle Scholar
  • 32 Lohrmann C, Zhang H, Thorek DL. et al. Cerenkov luminescence imaging for radiation dose calculation of a 90Y-labeled gastrin-releasing peptide receptor antagonist. J Nucl Med 2015; 56: 805-811.
    CrossrefPubMedGoogle Scholar
  • 33 Maeda J, Ji B, Irie T. et al. Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer’s disease enabled by positron emission tomography. J Neurosci 2007; 27: 10957-10968.
    CrossrefPubMedGoogle Scholar
  • 34 Mahmood U, Weissleder R. Near-infrared optical imaging of proteases in cancer. Mol Cancer Therap 2003; 2: 489-496.
    Google Scholar
  • 35 Maier FC, Wehrl HF, Schmid AM. et al. Longitudinal PET-MRI reveals [beta]-amyloid deposition and rCBF dynamics and connects vascular amyloidosis to quantitative loss of perfusion. Nat Med 2014; 20: 1485-1492.
    CrossrefPubMedGoogle Scholar
  • 36 Manook A, Yousefi BH, Willuweit A. et al. Small-animal PET imaging of amyloid-beta plaques with [11C]PiB and its multi-modal validation in an APP/PS1 mouse model of Alzheimer’s disease. PLoS One 2012; 7: e31310.
    CrossrefPubMedGoogle Scholar
  • 37 Monach PA, Mathis D, Benoist C. The K/BxN arthritis model. In: Coligan JE. et al. (eds). Current protocols in immunology. 2008 Chapter 15: Unit 15 22
    PubMedGoogle Scholar
  • 38 Ning X, Lee S, Wang Z. et al. Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity. Nat Mater 2011; 10: 602-607.
    CrossrefPubMedGoogle Scholar
  • 39 Pap T, Shigeyama Y, Kuchen S. et al. Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid arthritis. Arthritis Rheum 2000; 43: 1226-1232.
    CrossrefPubMedGoogle Scholar
  • 40 Raymond SB, Skoch J, Hills ID. et al. Smart optical probes for near-infrared fluorescence imaging of Alzheimer’s disease pathology. Eur J Nucl Med Mol Imaging 2008; 35 (Suppl. 01) S93-S98.
    CrossrefPubMedGoogle Scholar
  • 41 Robertson R, Germanos MS, Li C. et al. Optical imaging of Cerenkov light generation from positron-emitting radiotracers. Phys Med Biol 2009; 54: N355-N365.
    CrossrefPubMedGoogle Scholar
  • 42 Schwenck J, Griessinger CM, Fuchs K. et al. In vivo optical imaging of matrix metalloproteinase activity detects acute and chronic contact hypersensitivity reactions and enables monitoring of the antiinflammatory effects of N-acetylcysteine. Mol Imaging. 2014 13. doi: (PMID: 10.2310/7290.2014.00044)
    PubMedGoogle Scholar
  • 43 Shcherbakova DM, Verkhusha VV. Near-infrared fluorescent proteins for multicolor in vivo imaging. Nat Methods 2013; 10: 751-754.
    CrossrefPubMedGoogle Scholar
  • 44 Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res 2002; 4 (Suppl. 03) S265-272.
    CrossrefPubMedGoogle Scholar
  • 45 Snellman A, Lopez-Picon FR, Rokka J. et al. Longitudinal amyloid imaging in mouse brain with 11C-PIB: comparison of APP23, Tg2576, and APPswe-PS1dE9 mouse models of Alzheimer disease. J Nucl Med 2013; 54: 1434-1441.
    CrossrefPubMedGoogle Scholar
  • 46 Snellman A, Rokka J, Lopez-Picon FR. et al. Pharmacokinetics of [18F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2012; 39: 1784-1795.
    CrossrefPubMedGoogle Scholar
  • 47 Spinelli AE, Ferdeghini M, Cavedon C. et al. First human Cerenkography. J Biomed Opt 2013; 18: 20502.
    CrossrefPubMedGoogle Scholar
  • 48 Spinelli AE, Marengo M, Calandrino R. et al. Optical imaging of radioisotopes: a novel multimodal approach to molecular imaging. Q J Nucl Mol Imaging 2012; 56: 280-290.
    Google Scholar
  • 49 Sugiyama T, Kuroda S, Osanai T. et al. Near-infrared fluorescence labeling allows noninvasive tracking of bone marrow stromal cells transplanted into rat infarct brain. Neurosurgery 2011; 68: 1036-1047.
    CrossrefPubMedGoogle Scholar
  • 50 Sutton EJ, Boddington SE, Nedopil AJ. et al. An optical imaging method to monitor stem cell migration in a model of immune-mediated arthritis. Opt Express 2009; 17: 24403.
    CrossrefPubMedGoogle Scholar
  • 51 Thorek DL, Ogirala A, Beattie BJ. et al. Quantitative imaging of disease signatures through radioactive decay signal conversion. Nat Med 2013; 19: 1345-1350.
    CrossrefPubMedGoogle Scholar
  • 52 Thorek DL, Riedl CC, Grimm J. Clinical Cerenkov luminescence imaging of 18F-FDG. J Nucl Med 2014; 55: 95-98.
    CrossrefPubMedGoogle Scholar
  • 53 Timmermand OV, Tran TA, Strand SE. et al. Intratherapeutic biokinetic measurements, dosimetry parameter estimates, and monitoring of treatment efficacy using cerenkov luminescence imaging in preclinical radionuclide therapy. J Nucl Med 2015; 56: 444-449.
    CrossrefPubMedGoogle Scholar
  • 54 Tong H, Lou K, Wang W. Near-infrared fluorescent probes for imaging of amyloid plaques in Alzheimers disease. Acta Pharm Sin B 2015; 5: 25-33.
    CrossrefPubMedGoogle Scholar
  • 55 Vogl T, Eisenblatter M, Voller T. et al. Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity. Nat Commun 2014; 5: 4593.
    CrossrefPubMedGoogle Scholar
  • 56 von Reutern B, Grunecker B, Yousefi BH. et al. Voxel-based analysis of amyloid-burden measured with [11C]PiB PET in a double transgenic mouse model of Alzheimer’s disease. Mol Imaging Biol 2013; 15: 576-584.
    CrossrefPubMedGoogle Scholar
  • 57 Wang W, Shao R, Wu Q. et al. Targeting gelatinases with a near-infrared fluorescent cyclic His-Try-Gly-Phe peptide. Mol Imaging Biol 2009; 11: 424-433.
    CrossrefPubMedGoogle Scholar
  • 58 Weissleder R, Tung CH, Mahmood U. et al. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 1999; 17: 375-378.
    CrossrefPubMedGoogle Scholar
  • 59 Wolfs E, Holvoet B, Gijsbers R. et al. Optimization of multimodal imaging of mesenchymal stem cells using the human sodium iodide symporter for PET and Cerenkov luminescence imaging. PLoS ONE 2014; 9: e94833.
    CrossrefPubMedGoogle Scholar
  • 60 Xu Y, Liu H, Cheng Z. Harnessing the power of radionuclides for optical imaging: Cerenkov luminescence imaging. J Nucl Med 2011; 52: 2009-2018.
    CrossrefPubMedGoogle Scholar
  • 61 Yang M, Baranov E, Jiang P. et al. Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. Proc Natl Acad Sci USA 2000; 97: 1206-1211.
    CrossrefPubMedGoogle Scholar
  • 62 Ye Y, Akers W, Xu B. et al. Near-infrared fluorescent divalent RGD ligand for integrin alphavbeta(3)-targeted optical imaging. Bioorg Med Chem Lett 2012; 22: 5405-5409.
    CrossrefPubMedGoogle Scholar
  • 63 Zelmer A, Ward TH. Noninvasive fluorescence imaging of small animals. J Microsc 2013; 252: 8-15.
    CrossrefPubMedGoogle Scholar
  • 64 Zhang LW, Bäumer W, Monteiro-Riviere NA. Cellular uptake mechanisms and toxicity of quantum dots in dendritic cells. Nanomedicine 2011; 6: 777-791.
    CrossrefPubMedGoogle Scholar
  • 65 Zhang X, Kuo C, Moore A. et al. In vivo optical imaging of interscapular brown adipose tissue with 18F-FDG via Cerenkov luminescence imaging. PLoS One 2013; 8: e62007.
    CrossrefPubMedGoogle Scholar
  • 66 Zhang X, Tian Y, Zhang C. et al. Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease. Proc Natl Acad Sci USA 2015; 112: 9734-9739.
    CrossrefPubMedGoogle Scholar
  • 67 Zhang Y, Fan S, Yao Y. et al. In vivo near-infrared imaging of fibrin deposition in thromboembolic stroke in mice. PLoS One 2012; 7: e30262.
    CrossrefPubMedGoogle Scholar