İn vivo floresan görüntüleme ve in vivo uygulamalarda kullanılan florofor bileşikler

Year 2020, , 235 - 247, 21.01.2020

Erdal Tunç

https://doi.org/10.31362/patd.589329

Abstract

Bir dalga boyundaki ışıkla uyarıldığında, daha uzun dalga
boyunda ışık üreten maddelere (moleküllere/bileşiklere) floresan maddeler; bu
olguya floresan ışıma denir. Geleneksel olarak kültür ve hücre izlemelerinde
kullanılan floresan ışımaya dayalı görüntüleme teknikleri, son on-yıllarda in
vivo izlemelerde de kullanılmaya başlanmıştır. FLIM, FRET, FRI gibi in vivo
görüntüleme düzenekleri çoğunlukla küçük laboratuvar hayvanlarına uygulanırlar
ve ilgilenilen protein veya biyo-molekülün gerçek zaman-mekanda in vivo
görüntülerinin alınmasını olanaklı kılarlar. Bu düzenekler genel olarak,
hayvanın üzerine konacağı sahne,  bir
floresan uyarıcı ışık kaynağı,  gelen ve
emisyon ışık filtreleri, kamera aparatı (CCD kamera) ve dataları alıp analiz
eden bir yazılım programı elemanlarından oluşmaktadırlar. Herhangi bir in vivo
izleme sisteminde, öncelikle hedef protein ya bir doğal floresan reporter
proteinle kaynaştırılır ya da uygun görülen floresan boya (florofor bileşik)
ile kimyasal olarak işaretlenir; bundan sonra işaretli protein canlı bünyede
izlenir. Başarılı bir in vivo izleme için uygun floresan probun seçilmesi çok
önemlidir. İn vivo uygulamalarda kullanılan floresan problar genel olarak hedef
gözetmeyen problar, hedefli aktif problar, hedefli aktive edilebilen problar ve
nano-partiküller şeklinde sınıflandırılabilirler. Bu konudaki teknolojinin
ilerlemesi ve daha etkili floresan probların keşfedilmesi floresan ışımaya
dayalı in vivo izlemelerin daha yaygın olarak kullanılmalarına yol
açacaktır.  Bu izlemeler sayesinde
hastalıkların etiyoloji, prognoz ve tedavi süreçleri hakkında daha detaylı
bilgilere ulaşılacağı öngörülmektedir. Bu derlemede floresan ışımanın mekanizması, floresan
ışıma prensibine dayalı olarak çalışan ve önemli görülen in vivo görüntüleme
sistemleri ve florofor bileşikler hakkında bilgi verilmesi ve konuyla ilgili
önemli çalışmaların gözden geçirilmesi hedeflenmiştir. 

Keywords

floresan, prob, ışıma, görüntüleme, teknik

In vivo fluorescent imaging and fluorophores used in in-vivo applications

Abstract

Substances
that absorb light at specific wavelengths and emit light at longer wavelengths
are defined as fluorescent substances and this event is defined as
fluorescence. Fluorescence imaging techniques have conventionally been used in
culture and cell assays, but in the last decades those techniques have come
into use in in-vivo assays. In vivo fluorescent assay set-ups such as FLIM,
FRET, FRI, which are mostly applied to small laboratory animals, provide
spatiotemporal in vivo images of any protein or biomolecule. Those set-ups
constitute mainly from animal placement stage, convenient light source,
excitation and emission light filters, camera (charge couple device, CCD) and
data collecting and processing software components. For any fluorescent in vivo
assay system, firstly target protein is fused to a florescent reporter or bound
to appropriate fluorophore and then this fusion or tagged protein is visualized
in the body of live animal. Selection of proper fluorescent probe(s) are
vitally important for functionality of assay system. In vivo fluorescent probes
can be classified as non-targeting probes, active targeting probes, activable
targeting probes and fluorescent nanoparticles. Technological advancements in
this field and exploration of new effective fluorescent probes will further
generalize the use of fluorescence-based in-vivo assays which will provide deep
insights into etiology, prognosis and treatment aspects of diseases.  In this study, it was aimed to review
important studies and provide knowledge about general mechanism of
fluorescence, in-vivo applicable fluorophore compounds and some
fluorescence-based in vivo imaging techniques. 

Keywords

fluorescence, probe, emission, imaging, technique

References

• 1. Zhang X, Bloch S, Akers W, Achilefu S. Near-infrared molecular probes for in vivo imaging. Curr Protoc Cytom 2012;chapter 12:unit12.27. doi:10.1002/0471142956.cy1227s60.
• 2. Tung CH. Fluorescent peptide probes for in vivo diagnostic imaging. Biopolymers 2004;76:391-403. DOI 10.1002/bip.20139.
• 3. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P, eds. Molecular biology of the cell. In: visualizing cells. 5th ed. New York: Garland Science, Taylor & Francis Group, 2008;582-587.
• 4. Li Q, Tang Y, Hu W, Li Z. Fluorescence of nonaromatic organic systems and room temperature phosphorescence of organic luminogens: the intrinsic principle and recent progress. Small 2018;14:e1801560. doi: 10.1002/smll.201801560.
• 5. https://application.wiley-vch.de/books/sample/3527316698_c01.pdf. Erişim tarihi 18 Mart 2019.
• 6. Süel G. Use of fluorescence microscopy to analyze genetic circuit dynamics. Methods Enzymol 2011;497:275-93. DOI: 10.1016/B978-0-12-385075-1.00013-5.
• 7. Suhling K, Hirvonena LM, Levitt JA et al. Fluorescence lifetime imaging (FLIM): basic concepts and some recent developments. Med Photon 2015;27:3-40. http://dx.doi.org/10.1016/j.medpho.2014.12.001.
• 8. Haustein E, Schwille P. Trends in fluorescence imaging and related techniques to unravel biological information. HFSP J 2007;1:169–180. doi: 10.2976/1.2778852. doi: 10.1117/1.JBO.23.9.091415.
• 9. Sauer L, Andersen KM, Dysli C, Zinkernagel MS, Bernstein PS, Hammer M. Review of clinical approaches in fluorescence lifetime imaging ophthalmoscopy. J Biomed Opt 2018;23:1-20. doi: 10.1117/1.JBO.23.9.091415.
• 10. Donya M, Radford M, ElGuindy A, Firmin D, Yacoub MH. Radiation in medicine: origins, risks and aspirations. Glob Cardiol Sci Pract 2014;2014:437–448. doi: 10.5339/gcsp.2014.57.
• 11. https://www.salk.edu/pdf/fluorochrome-table.html. Erişim tarihi 03 Mayıs 2019.
• 12. Fenton KE, Martirosyan NL, Abdelwahab MG, Coons SW, Preul MC, Scheck AC. In vivo visualization of GL261-luc2 mouse glioma cells by use of Alexa Fluor-labeled TRP-2 antibodies. Neurosurg Focus 2014;36:E12. doi: 10.3171/2013.12.FOCUS13488.
• 13. Yoneya S, Saito T, Komatsu Y, Koyama I, Takahashi K, Duvoll-Young J. Binding properties of indocyanine green in human blood. Invest Ophthalmol Vis Sci 1998;39:1286-90.
• 14. Yuan B, Chen NG, Zhu Q. Emission and absorption properties of indocyanine green in Intralipid solution. J Biomed Opt 2004;9:497–503. DOI: 10.1117/1.1695411.
• 15. Alander JT, Kaartinen I, Laakso A et al. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging 2012;2012:940585. doi:10.1155/2012/940585.
• 16. Hassan M, Riley J, Chernomordik V et al. Fluorescence lifetime imaging system for in vivo studies. Mol Imaging 2007;6:229–236.
• 17. Miao Y, Gu C, Zhu Y, Yu B, Shen Y, Cong H. Recent progress in fluorescence imaging of the near-infrared II window. Chembiochem 2018;19:2522-2541. DOI: 10.1002/cbic.201800466.
• 18. Rao J, Dragulescu-Andrasi A, Yao H. Fluorescence imaging in vivo: recent advances. Curr Opin Biotechnol 2007;18:17-25. DOI 10.1016/j.copbio.2007.01.003.
• 19. Dancik Y, Favre A, Loy CJ, Zvyagin AV, Roberts MS. Use of multiphoton tomography and fluorescence lifetime imaging to investigate skin pigmentation in vivo. J Biomed Opt 2013;18:26022. doi: 10.1117/1.JBO.18.2.026022.
• 20. Chorvat D Jr., Chorvatova A. Multi-wavelength fluorescence lifetime spectroscopy: a new approach to the study of endogenous fluorescence in living cells and tissues. Laser Phys Lett 2009;6:175–193. DOI 10.1002/lapl.200810132.
• 21. Won Y, Park B, Kim I, Lee S. Fluorescence lifetime measurement with confocal endomicroscopy for direct analysis of tissue biochemistry in vivo. 2016:2;e00139. doi: 10.1016/j.heliyon.2016.e00139.
• 22. De Los Santos C, Chang CW, Mycek MA, Cardullo RA. FRAP, FLIM, and FRET: detection and analysis of cellular dynamics on a molecular scale using fluorescence microscopy. Mol Reprod Dev 2015;82:587–604. doi:10.1002/mrd.22501.
• 23. Becker W. Fluorescence lifetime imaging--techniques and applications. J Microsc 2012;247:119-36. doi: 10.1111/j.1365-2818.2012.03618.x.
• 24. Fruhwirth GO, Matthews DR, Brock A et al. Deep-tissue multi-photon fluorescence lifetime microscopy for intravital imaging of protein-protein interactions. Proc of SPIE 2009;7183:71830L-1. doi: 10.1117/12.817129.
• 25. Fruhwirth GO, Fernandes LP, Weitsman G et al. How Förster resonance energy transfer imaging improves the understanding of protein interaction networks in cancer biology. Chemphyschem 2011;12:442-61. DOI: 10.1002/cphc.201000866.
• 26. Kaminski CF, Rees EJ, Schierle GS. A quantitative protocol for intensity-based live cell FRET imaging. Methods Mol Biol 2014;1076:445-54. doi: 10.1007/978-1-62703-649-8_19.
• 27. Ma T, Hou Y, Zeng J et al. Dual-ratiometric target-triggered fluorescent probe for simultaneous quantitative visualization of tumor microenvironment protease activity and pH in vivo. J Am Chem Soc 2018;140:211-218. DOI: 10.1021/jacs.7b08900.
• 28. Stockert JC, Blázquez-Castro A (2017). Fluorescence microscopy in life sciences. In: chapter 3 dyes and fluorochromes. Bentham e-books, Bentham Science Publishers, 2017;61-95. https://books.google.com.tr/books. Erişim tarihi 08.07.2019.
• 29. Freidus LG, Pradeep P, Kumar P, Choonara YE, Pillay V. Alternative fluorophores designed for advanced molecular imaging. Drug Discov Today 2018;23:115-133. doi: 10.1016/j.drudis.2017.09.008.
• 30. Fu H, Cui M, Zhao L et al. Highly sensitive near-infrared fluorophores for in vivo detection of amyloid-β plaques in alzheimer's disease. J Med Chem 2015;58:6972-83. DOI: 10.1021/acs.jmedchem.5b00861.
• 31. Park GK, Lee JH, Levitz A, El Fakhri G, Hwang NS, Henary M, Choi HS. Lysosome-targeted bioprobes for sequential cell tracking from macroscopic to microscopic scales. Adv Mater 2019;31:e1806216. DOI: 10.1002/adma.201806216.
• 32. Pedro Carvalho PHPR, Correa JR, Guido BC et al. Designed benzothiadiazole fluorophores for selective mitochondrial imaging and dynamics. Chem Eur J 2014; 20:15360-15374. DOI: 10.1002/chem.201404039.
• 33. Zhang Q, Tian X, Zhou H, Wu J, Tian Y. Lighting the way to see inside two-photon absorption materials: structure-property relationship and biological imaging. Materials (Basel) 2017;10;E223. doi:10.3390/ma10030223.
• 34. Kulkarni RU, Vandenberghe M, Thunemann M et al. In vivo two-photon voltage imaging with sulfonated rhodamine dyes. ACS Cent Sci 2018;4:1371-1378. DOI: 10.1021/acscentsci.8b00422.
• 35. Altınoǧlu EI, Russin TJ, Kaiser JM et al. Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer. ACS Nano 2008;2:2075-2084. doi: 10.1021/nn800448r.
• 36. Tosi G, Bondioli L, Ruozi B et al. NIR-labeled nanoparticles engineered for brain targeting: in vivo optical imaging application and fluorescent microscopy evidences. J Neural Transm 2011;118:145-153. doi: 10.1007/s00702-010-0497-1.
• 37. Alford R, Simpson HM, Duberman J et al. Toxicity of organic fluorophores used in molecular imaging: literature review. Mol Imaging 2009;8:341-54. DOI 10.2310/7290.2009.00031.
• 38. Nesterov EE, Skoch J, Hyman BT, Klunk WE, Bacskai BJ, Swager TM. In vivo optical imaging of amyloid aggregates in brain: design of fluorescent markers. Angew Chem Int Ed 2005;44:5452-5456. DOI: 10.1002/anie.200500845.
• 39. Baea S, Lima E, Hwang D, Huh H, Kim SK. Torsion-dependent fluorescence switching of amyloid-binding dye NIAD-4. Chemical Physics Letters 2015;633:109-113. http://dx.doi.org/10.1016/j.cplett.2015.05.010.
• 40. Lindhoud S, Westphal AH, Visser AJWG, Borst JW, van Mierlo CPM. Fluorescence of Alexa Fluor dye tracks protein folding. PLoS One 2012;7:e46838. doi: 10.1371/journal.pone.0046838.
• 41. Hayashi-Takanaka Y, Stasevich TJ, Kurumizaka H, Nozaki N, Kimura H. Evaluation of chemical fluorescent dyes as a protein conjugation partner for live cell imaging. PLoS One 2014;9:e106271. doi:10.1371/journal.pone.0106271.
• 42. Rai S, Bhardwaj U, Misra A, Singh S, Gupta R. Comparison between photostability of Alexa Fluor 448 and Alexa Fluor 647 with conventional dyes FITC and APC by flow cytometry. Int J Lab Hem 2018;40:e52–e54. DOI: 10.1111/ijlh.12809.
• 43. Giedt RJ, Koch PD, Weissleder R. Single cell analysis of drug distribution by intravital imaging. PLoS One 2013;8:e60988. doi:10.1371/journal.pone.0060988.
• 44. https://www.thermofisher.com/tr/en/home/references/molecular-probes-the-handbook/fluorophores-and-their-amine-reactive-derivatives/bodipy-dye-series.html. Erişim tarihi 21Mayıs 2019.
• 45. http://www.emu.uct.ac.za/sites/default/files/image_tool/images/430/lecture-4-intracellular-localisation/actin.pdf. Erişim tarihi 21 Mayıs 2019.
• 46. Liu S, Lin TP, Li D et al. Lewis acid-assisted isotopic 18F-19F exchange in BODIPY dyes: facile generation of positron emission tomography/fluorescence dual modality agents for tumor imaging. Theranostics 2013;3:181-9. doi: 10.7150/thno.5984.
• 47. Lee KH, Nam H, Won JS et al. In vivo spinal distribution of Cy5.5 fluorescent dye after injection via the lateral ventricle and cisterna magna in rat model. J Korean Neurosurg Soc 2018;61:434-440. doi: 10.3340/jkns.2017.0252.
• 48. Robertson TA, Bunel F, Roberts MS. Fluorescein derivatives in intravital fluorescence imaging. Cells 2013;2:591-606. doi:10.3390/cells2030591.
• 49. Mottram L, Boonyarattanakalin S, Kovel RE, Peterson BR. The Pennsylvania Green Fluorophore: a hybrid of Oregon Green and Tokyo Green for the construction of hydrophobic and pH-insensitive molecular probes. Org Lett 2006;8:581–584. doi:10.1021/ol052655g.
• 50. Cirillo G, Luca DD, Papa M. Calcium imaging of living astrocytes in the mouse spinal cord following sensory stimulation. Neural Plast 2012;2012:425818. doi:10.1155/2012/425818
• 51. Grimm JB, Heckman LM, Lavis LD. The chemistry of small-molecule fluorogenic probes. Prog Mol Biol Transl Sci 2013;113:1-34. doi: 10.1016/B978-0-12-386932-6.00001-6.
• 52. Beija M, Afonso CAM, Martinho JMG. Synthesis and applications of Rhodamine derivatives as fluorescent probes. Chem Soc Rev 2009;38:2410-2433. DOI: 10.1039/b901612k.
• 53. Zhang Y, Guo S, Jiang Z, Mao G, Ji X, He Z. Rox-DNA functionalized silicon nanodots for ratiometric detection of mercury ions in live cells. Anal Chem 2018;90:9796-9804. DOI: 10.1021/acs.analchem.8b01574.
• 54. Hama Y, Urano Y, Koyama Y, Gunn AJ, Choyke PL, Kobayashi H. A self-quenched galactosamine-serum albumin-rhodamineX conjugate: a "smart" fluorescent molecular imaging probe synthesized with clinically applicable material for detecting peritoneal ovarian cancer metastases. Clin Cancer Res 2007;13:6335-43. doi:10.1158/1078-0432.CCR-07-1004.
• 55. Thomas TP, Myaing MT, Ye JY et al. Detection and analysis of tumor fluorescence using a two-photon optical fiber probe. Biophys J 2004;86:3959-65. doi: 10.1529/biophysj.103.034462.
• 56. Whitaker JE, Haugland RP, Ryan D, Hewitt PC, Haugland RP, Prendergast FG. Fluorescent rhodol derivatives: versatile, photostable labels and tracers. Anal Biochem 1992;207:267-79. DOI: 10.1016/0003-2697(92)90011-u.
• 57. Poronik YM, Clermont G, Blanchard-Desce M, Gryko DT. Nonlinear optical chemosensor for sodium ion based on rhodol chromophore. J Org Chem 2013;78:11721-32. DOI: 10.1021/jo401653t.
• 58. Li L, Wang S, Lan H et al. Rhodol derivatives as selective fluorescent probes for the detection of HgII ions and the bioimaging of hypochlorous acid. ChemistryOpen 2018;7:136-143. DOI: 10.1002/open.201700154.
• 59. Miller DR, Hassan AM, Jarrett JW et al. In vivo multiphoton imaging of a diverse array of fluorophores to investigate deep neurovascular structure. Biomed Opt Express 2017;8:3470-3481. doi: 10.1364/BOE.8.003470.
• 60. Cho H, Bhatti FU, Lee S, Brand DD, Yi AK, Hasty KA. In vivo dual fluorescence imaging to detect joint destruction. Artif Organs 2016;40:1009-1013. doi: 10.1111/aor.12685.