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Practical Guidance for Developing Small-Molecule Optical Probes for In Vivo Imaging

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Abstract

The WMIS Education Committee (2019–2022) reached a consensus that white papers on molecular imaging could be beneficial for practitioners of molecular imaging at their early career stages and other scientists who are interested in molecular imaging. With this consensus, the committee plans to publish a series of white papers on topics related to the daily practice of molecular imaging. In this white paper, we aim to provide practical guidance that could be helpful for optical molecular imaging, particularly for small molecule probe development and validation in vitro and in vivo. The focus of this paper is preclinical animal studies with small-molecule optical probes. Near-infrared fluorescence imaging, bioluminescence imaging, chemiluminescence imaging, image-guided surgery, and Cerenkov luminescence imaging are discussed in this white paper.

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  1. FDA approves new imaging drug to help identify ovarian cancer lesions 2021.

References

  1. Massoud TF, Gambhir SS (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17:545–580. https://doi.org/10.1101/gad.1047403

    Article  CAS  PubMed  Google Scholar 

  2. Jaffer FA, Weissleder R (2005) Molecular imaging in the clinical arena. JAMA 293:855–862. https://doi.org/10.1001/jama.293.7.855

    Article  CAS  PubMed  Google Scholar 

  3. Ahn BC (2011) Applications of molecular imaging in drug discovery and development process. Curr Pharm Biotechnol 12:459–468

    Article  CAS  PubMed  Google Scholar 

  4. Contag PR (2002) Whole-animal cellular and molecular imaging to accelerate drug development. Drug Disc Today 7:555–562

    Article  CAS  Google Scholar 

  5. Hintersteiner M, Enz A, Frey P, Jaton AL, Kinzy W, Kneuer R, Neumann U, Rudin M, Staufenbiel M, Stoeckli M et al (2005) In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe. Nat Biotechnol 23:577–583. https://doi.org/10.1038/nbt1085

    Article  CAS  PubMed  Google Scholar 

  6. Weissleder R ed. Molecular imaging: principles and practice. Shelton, CT: People’s Medical Publishing House–USA; 2010.

  7. Talebloo N, Gudi M, Robertson N, Wang P (2020) Magnetic particle imaging: current applications in biomedical research. J Magn Reson Imaging 51:1659–1668. https://doi.org/10.1002/jmri.26875

    Article  PubMed  Google Scholar 

  8. Chandrasekharan P, Tay ZW, Zhou XY, Yu E, Orendorff R, Hensley D, Huynh Q, Fung KLB, VanHook CC, Goodwill P et al (2018) A perspective on a rapid and radiation-free tracer imaging modality, magnetic particle imaging, with promise for clinical translation. Br J Radiol 91:20180326. https://doi.org/10.1259/bjr.20180326

    Article  PubMed  PubMed Central  Google Scholar 

  9. Attia ABE, Balasundaram G, Moothanchery M, Dinish US, Bi R, Ntziachristos V, Olivo M (2019) A review of clinical photoacoustic imaging: current and future trends. Photoacoustics 16:100144. https://doi.org/10.1016/j.pacs.2019.100144

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ray P (2011) Multimodality molecular imaging of disease progression in living subjects. J Biosci 36:499–504. https://doi.org/10.1007/s12038-011-9079-0

    Article  PubMed  Google Scholar 

  11. Hong G, Antaris A, Dai H (2017) Near-infrared fluorophores for biomedical imaging. Nature Biomed Eng 1:0010

    Article  CAS  Google Scholar 

  12. Bednar B, Zhang GJ, Williams DL Jr, Hargreaves R, Sur C (2007) Optical molecular imaging in drug discovery and clinical development. Expert Opin Drug Discov 2:65–85. https://doi.org/10.1517/17460441.2.1.65

    Article  CAS  PubMed  Google Scholar 

  13. Rudin M, Weissleder R (2003) Molecular imaging in drug discovery and development. Nat Rev Drug Discov 2:123–131. https://doi.org/10.1038/nrd1007

    Article  CAS  PubMed  Google Scholar 

  14. Rao J, Dragulescu-Andrasi A, Yao H (2007) Fluorescence imaging in vivo: recent advances. Curr Opin Biotechnol 18:17–25. https://doi.org/10.1016/j.copbio.2007.01.003

    Article  CAS  PubMed  Google Scholar 

  15. Ntziachristos V, Bremer C, Weissleder R (2003) Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging. Eur Radiol 13:195–208. https://doi.org/10.1007/s00330-002-1524-x

    Article  PubMed  Google Scholar 

  16. Lakowicz J (1999) Principles of fluorescence spectroscopy. Plenum Publishing Corporation.

  17. Villringer A, Planck J, Hock C, Schleinkofer L, Dirnagl U (1993) Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults. Neurosci Lett 154:101–104. https://doi.org/10.1016/0304-3940(93)90181-j

    Article  CAS  PubMed  Google Scholar 

  18. Mitchell GS, Gill RK, Boucher DL, Li C, Cherry SR (2011) In vivo Cerenkov luminescence imaging: a new tool for molecular imaging. Philos Transact A Math Phys Eng Sci 369:4605–4619. https://doi.org/10.1098/rsta.2011.0271

    Article  CAS  Google Scholar 

  19. Miao Q, Xie C, Zhen X, Lyu Y, Duan H, Liu X, Jokerst JV, Pu K (2017) Molecular afterglow imaging with bright, biodegradable polymer nanoparticles. Nat Biotechnol 35:1102–1110. https://doi.org/10.1038/nbt.3987

    Article  CAS  PubMed  Google Scholar 

  20. Hu Z, Chen WH, Tian J, Cheng Z (2020) NIRF nanoprobes for cancer molecular imaging: approaching clinic. Trends Mol Med 26:469–482. https://doi.org/10.1016/j.molmed.2020.02.003

    Article  CAS  PubMed  Google Scholar 

  21. Perumal V, Sivakumar PM, Zarrabi A, Muthupandian S, Vijayaraghavalu S, Sahoo K, Das A, Das S, Payyappilly SS, Das S (2019) Near infra-red polymeric nanoparticle based optical imaging in cancer diagnosis. J Photochem Photobiol B. 199:111630. https://doi.org/10.1016/j.jphotobiol.2019.111630

    Article  CAS  PubMed  Google Scholar 

  22. Kim J, Lee N, Hyeon T (2017) Recent development of nanoparticles for molecular imaging. Philos Trans A Math Phys Eng Sci. 375. https://doi.org/10.1098/rsta.2017.0022

  23. Yu J, Zhang X, Hao X, Zhang X, Zhou M, Lee CS, Chen X (2014) Near-infrared fluorescence imaging using organic dye nanoparticles. Biomater 35:3356–3364. https://doi.org/10.1016/j.biomaterials.2014.01.004

    Article  CAS  Google Scholar 

  24. Li J, Rao J, Pu K (2018) Recent progress on semiconducting polymer nanoparticles for molecular imaging and cancer phototherapy. Biomater 155:217–235. https://doi.org/10.1016/j.biomaterials.2017.11.025

    Article  CAS  Google Scholar 

  25. Shu X, Royant A, Lin MZ, Aguilera TA, Lev-Ram V, Steinbach PA, Tsien RY (2009) Mammalian expression of infrared fluorescent proteins engineered from a bacterial phytochrome. Sci 324:804–807. https://doi.org/10.1126/science.1168683

    Article  Google Scholar 

  26. Baloban M, Shcherbakova DM, Pletnev S, Pletnev VZ, Lagarias JC, Verkhusha VV (2017) Designing brighter near-infrared fluorescent proteins: insights from structural and biochemical studies. Chem Sci 8:4546–4557. https://doi.org/10.1039/c7sc00855d

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Filonov GS, Piatkevich KD, Ting LM, Zhang J, Kim K, Verkhusha VV (2011) Bright and stable near-infrared fluorescent protein for in vivo imaging. Nat Biotechnol 29:757–761. https://doi.org/10.1038/nbt.1918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Shcherbakova DM, Verkhusha VV (2013) Near-infrared fluorescent proteins for multicolor in vivo imaging. Nat Methods 10:751–754. https://doi.org/10.1038/nmeth.2521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Matlashov ME, Shcherbakova DM, Alvelid J, Baloban M, Pennacchietti F, Shemetov AA, Testa I, Verkhusha VV (2020) A set of monomeric near-infrared fluorescent proteins for multicolor imaging across scales. Nat Commun 11:239. https://doi.org/10.1038/s41467-019-13897-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tsien RY (1998) The green fluorescent protein. Annu Rev Biochem 67:509–544. https://doi.org/10.1146/annurev.biochem.67.1.509

    Article  CAS  PubMed  Google Scholar 

  31. Shaner NC, Steinbach PA, Tsien RY (2005) A guide to choosing fluorescent proteins. Nat Methods 2:905–909. https://doi.org/10.1038/nmeth819

    Article  CAS  PubMed  Google Scholar 

  32. Avci P, Gupta A, Sadasivam M, Vecchio D, Pam Z, Pam N, Hamblin MR (2013) Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring. Semin Cutan Med Surg. 32:41–52

    PubMed  PubMed Central  Google Scholar 

  33. Zhang X, Ran C (2013) Dual functional small molecule probes as fluorophore and ligand for misfolding proteins. Curr Org Chem 17:580–593. https://doi.org/10.2174/1385272811317060004

    Article  CAS  Google Scholar 

  34. Arlauckas SP, Kumar M, Popov AV, Poptani H, Delikatny EJ (2017) Near infrared fluorescent imaging of choline kinase alpha expression and inhibition in breast tumors. Oncotarget 8:16518–16530. https://doi.org/10.18632/oncotarget.14965

    Article  PubMed  PubMed Central  Google Scholar 

  35. Hermanson GT. Fluorescent probes (2013) In: Bioconjugate techniques. Academic Press; 395–463.

  36. Olson MT, Ly QP, Mohs AM (2019) Fluorescence guidance in surgical oncology: challenges, opportunities, and translation. Mol Imaging Biol 21:200–218. https://doi.org/10.1007/s11307-018-1239-2

    Article  PubMed  PubMed Central  Google Scholar 

  37. Belykh E, Martirosyan NL, Yagmurlu K, Miller EJ, Eschbacher JM, Izadyyazdanabadi M, Bardonova LA, Byvaltsev VA, Nakaji P, Preul MC (2016) Intraoperative fluorescence imaging for personalized brain tumor resection: current state and future directions. Front Surg 3:55. https://doi.org/10.3389/fsurg.2016.00055

    Article  PubMed  PubMed Central  Google Scholar 

  38. Ash C, Dubec M, Donne K, Bashford T (2017) Effect of wavelength and beam width on penetration in light-tissue interaction using computational methods. Lasers Med Sci 32:1909–1918. https://doi.org/10.1007/s10103-017-2317-4

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ueno T, Nagano T (2011) Fluorescent probes for sensing and imaging. Nat Methods 8:642–645. https://doi.org/10.1038/nmeth.1663

    Article  CAS  PubMed  Google Scholar 

  40. Lavis LD, Raines RT (2008) Bright ideas for chemical biology. ACS Chem Biol 3:142–155. https://doi.org/10.1021/cb700248m

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fu Y, Finney NS (2018) Small-molecule fluorescent probes and their design. RSC Adv 8:29051–29061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Horváth P, Šebej P, Šolomek T, Klán P (2015) Small-molecule fluorophores with large stokes shifts: 9-iminopyronin analogues as clickable tags. J Org Chem 80:1299–1311. https://doi.org/10.1021/jo502213t

    Article  CAS  PubMed  Google Scholar 

  43. Zheng Q, Juette MF, Jockusch S, Wasserman MR, Zhou Z, Altman RB, Blanchard SC (2014) Ultra-stable organic fluorophores for single-molecule research. Chem Soc Rev 43:1044–1056. https://doi.org/10.1039/c3cs60237k

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hudson GA, Cheng L, Yu J, Yan Y, Dyer DJ, McCarroll ME, Wang L (2010) Computational studies on response and binding selectivity of fluorescence sensors. J Phys Chem B 114:870–876. https://doi.org/10.1021/jp908368k

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chen C, Baranov MS, Zhu L, Baleeva NS, Smirnov AY, Zaitseva SO, Yampolsky IV, Solntsev KM, Fang C (2019) Designing redder and brighter fluorophores by synergistic tuning of ground and excited states. Chem Commun (Camb) 55:2537–2540. https://doi.org/10.1039/c8cc10007a

    Article  CAS  PubMed  Google Scholar 

  46. Grimm JB, Xie L, Casler JC, Patel R, Tkachuk AN, Falco N, Choi H, Lippincott-Schwartz J, Brown TA, Glick BS et al (2021) A general method to improve fluorophores using deuterated auxochromes. JACS Au 1:690–696. https://doi.org/10.1021/jacsau.1c00006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Koide Y, Urano Y, Hanaoka K, Terai T, Nagano T (2011) Development of an Si-rhodamine-based far-red to near-infrared fluorescence probe selective for hypochlorous acid and its applications for biological imaging. J Am Chem Soc 133:5680–5682. https://doi.org/10.1021/ja111470n

    Article  CAS  PubMed  Google Scholar 

  48. Yuan L, Lin W, Zheng K, He L, Huang W (2013) Far-red to near infrared analyte-responsive fluorescent probes based on organic fluorophore platforms for fluorescence imaging. Chem Soc Rev 42:622–661. https://doi.org/10.1039/c2cs35313j

    Article  CAS  PubMed  Google Scholar 

  49. Conley NR, Dragulescu-Andrasi A, Rao J, Moerner WE (2012) A selenium analogue of firefly D-luciferin with red-shifted bioluminescence emission. Angew Chem Int Ed Engl 51:3350–3353. https://doi.org/10.1002/anie.201105653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Qian K, Qu C, Ma X, Chen H, Kandawa-Schulz M, Song W, Miao W, Wang Y, Cheng Z (2020) Tuning the near infrared II emitting wavelength of small molecule dyes by single atom alteration. Chem Commun 56:523–526. https://doi.org/10.1039/C9CC08434G

    Article  CAS  Google Scholar 

  51. Shao Y, Zhang X, Liang K, Wang J, Lin Y, Yang S, Zhang W-B, Zhu M, Sun B (2017) How does the interplay between bromine substitution at bay area and bulky substituents at imide position influence the photophysical properties of perylene diimides? RSC Adv 7:16155–16162. https://doi.org/10.1039/C7RA00779E

    Article  CAS  Google Scholar 

  52. Baggaley E, Weinstein JA, Williams JAG (2012) Lighting the way to see inside the live cell with luminescent transition metal complexes. Coord Chem Rev 256:1762–1785. https://doi.org/10.1016/j.ccr.2012.03.018

    Article  CAS  Google Scholar 

  53. Ning Y, Cheng S, Wang JX, Liu YW, Feng W, Li F, Zhang JL (2019) Fluorescence lifetime imaging of upper gastrointestinal pH in vivo with a lanthanide based near-infrared τ probe. Chem Sci 10:4227–4235. https://doi.org/10.1039/c9sc00220k

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Weissleder R (2001) A clearer vision for in vivo imaging. Nat Biotechnol 19:316–317. https://doi.org/10.1038/86684

    Article  CAS  PubMed  Google Scholar 

  55. Fewell MP, von Trojan A (2019) Absorption of light by water in the region of high transparency: recommended values for photon-transport calculations. Appl Opt 58:2408–2421. https://doi.org/10.1364/AO.58.002408

    Article  CAS  PubMed  Google Scholar 

  56. Antaris AL, Chen H, Cheng K, Sun Y, Hong G, Qu C, Diao S, Deng Z, Hu X, Zhang B et al (2016) A small-molecule dye for NIR-II imaging. Nat Mater 15:235–242. https://doi.org/10.1038/nmat4476

    Article  CAS  PubMed  Google Scholar 

  57. Zhu S, Tian R, Antaris AL, Chen X, Dai H (2019) Near-infrared-II molecular dyes for cancer imaging and surgery. Adv Mater. 31:e1900321. https://doi.org/10.1002/adma.201900321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. He S, Song J, Qu J, Cheng Z (2018) Crucial breakthrough of second near-infrared biological window fluorophores: design and synthesis toward multimodal imaging and theranostics. Chem Soc Rev 47:4258–4278. https://doi.org/10.1039/c8cs00234g

    Article  CAS  PubMed  Google Scholar 

  59. Sandell JL, Zhu TC (2011) A review of in-vivo optical properties of human tissues and its impact on PDT. J Biophotonics 4:773–787. https://doi.org/10.1002/jbio.201100062

    Article  PubMed  PubMed Central  Google Scholar 

  60. Patterson AP, Booth SA, Saba R (2014) The emerging use of in vivo optical imaging in the study of neurodegenerative diseases. Biomed Res Int. 2014:401306. https://doi.org/10.1155/2014/401306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Monici M (2005) Cell and tissue autofluorescence research and diagnostic applications. Biotechnol Annu Rev 11:227–256. https://doi.org/10.1016/S1387-2656(05)11007-2

    Article  CAS  PubMed  Google Scholar 

  62. Croce AC, Bottiroli G (2014) Autofluorescence spectroscopy and imaging: a tool for biomedical research and diagnosis. Eur J Histochem 58:2461. https://doi.org/10.4081/ejh.2014.2461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Hoffman RM, Yang M (2006) Whole-body imaging with fluorescent proteins. Nat Protoc 1:1429–1438. https://doi.org/10.1038/nprot.2006.223

    Article  CAS  PubMed  Google Scholar 

  64. Welvaert M, Rosseel Y (2013) On the definition of signal-to-noise ratio and contrast-to-noise ratio for FMRI data. PLoS One. 8:e77089. https://doi.org/10.1371/journal.pone.0077089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Yang C, Zhang J, Peng WT, Sheng W, Liu D, Kuttipillai PS, Young M, Donahue MR, Levine BG, Borhan B et al (2018) Impact of stokes shift on the performance of near-infrared harvesting transparent luminescent solar concentrators. Sci Rep 8:16359. https://doi.org/10.1038/s41598-018-34442-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Troy T, Jekic-McMullen D, Sambucetti L, Rice B (2004) Quantitative comparison of the sensitivity of detection of fluorescent and bioluminescent reporters in animal models. Mol Imaging 3:9–23. https://doi.org/10.1162/153535004773861688

    Article  CAS  PubMed  Google Scholar 

  67. Mansfield JR, Gossage KW, Hoyt CC, Levenson RM (2005) Autofluorescence removal, multiplexing, and automated analysis methods for in-vivo fluorescence imaging. J Biomed Opt 10:41207. https://doi.org/10.1117/1.2032458

    Article  CAS  PubMed  Google Scholar 

  68. Mansfield JR (2010) Distinguished photons: a review of in vivo spectral fluorescence imaging in small animals. Curr Pharm Biotechnol 11:628–638. https://doi.org/10.2174/138920110792246474

    Article  CAS  PubMed  Google Scholar 

  69. Kobayashi H, Ogawa M, Alford R, Choyke PL, Urano Y (2010) New strategies for fluorescent probe design in medical diagnostic imaging. Chem Rev 110:2620–2640. https://doi.org/10.1021/cr900263j

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Chen K, Chen X (2010) Design and development of molecular imaging probes. Curr Top Med Chem 10:1227–1236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Eppstein MJ, Hawrysz DJ, Godavarty A, Sevick-Muraca EM (2002) Three-dimensional, Bayesian image reconstruction from sparse and noisy data sets: near-infrared fluorescence tomography. Proc Natl Acad Sci U S A 99:9619–9624. https://doi.org/10.1073/pnas.112217899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Dang X, Bardhan NM, Qi J, Gu L, Eze NA, Lin CW, Kataria S, Hammond PT, Belcher AM (2019) Deep-tissue optical imaging of near cellular-sized features. Sci Rep 9:3873. https://doi.org/10.1038/s41598-019-39502-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ran C, Xu X, Raymond SB, Ferrara BJ, Neal K, Bacskai BJ, Medarova Z, Moore A (2009) Design, synthesis, and testing of difluoroboron-derivatized curcumins as near-infrared probes for in vivo detection of amyloid-beta deposits. J Am Chem Soc 131:15257–15261. https://doi.org/10.1021/ja9047043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Cui M, Ono M, Watanabe H, Kimura H, Liu B, Saji H (2014) Smart near-infrared fluorescence probes with donor-acceptor structure for in vivo detection of beta-amyloid deposits. J Am Chem Soc 136:3388–3394. https://doi.org/10.1021/ja4052922

    Article  CAS  PubMed  Google Scholar 

  75. Chen C, Tian R, Zeng Y, Chu C, Liu G (2020) Activatable fluorescence probes for “turn-on” and ratiometric biosensing and bioimaging: from NIR-I to NIR-II. Bioconjug Chem 31:276–292. https://doi.org/10.1021/acs.bioconjchem.9b00734

    Article  CAS  PubMed  Google Scholar 

  76. Weissleder R, Tung CH, Mahmood U, Bogdanov A Jr (1999) In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 17:375–378. https://doi.org/10.1038/7933

    Article  CAS  PubMed  Google Scholar 

  77. Mawn TM, Popov AV, Beardsley NJ, Stefflova K, Milkevitch M, Zheng G, Delikatny EJ (2011) In vivo detection of phospholipase C by enzyme-activated near-infrared probes. Bioconjug Chem 22:2434–2443. https://doi.org/10.1021/bc200242v

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Chiorazzo MG, Tunset HM, Popov AV, Johansen B, Moestue S, Delikatny EJ (2019) Detection and differentiation of breast cancer sub-types using a cPLA2alpha activatable fluorophore. Sci Rep 9:6122. https://doi.org/10.1038/s41598-019-41626-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Liu HW, Chen L, Xu C, Li Z, Zhang H, Zhang XB, Tan W (2018) Recent progresses in small-molecule enzymatic fluorescent probes for cancer imaging. Chem Soc Rev 47:7140–7180. https://doi.org/10.1039/c7cs00862g

    Article  CAS  PubMed  Google Scholar 

  80. Liebov BK, Arroyo AD, Rubtsova NI, Osharovich SA, Delikatny EJ, Popov AV (2018) Nonprotecting group synthesis of a phospholipase C activatable probe with an azo-free quencher. ACS Omega 3:6867–6873. https://doi.org/10.1021/acsomega.8b00635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Urano Y, Sakabe M, Kosaka N, Ogawa M, Mitsunaga M, Asanuma D, Kamiya M, Young MR, Nagano T, Choyke PL et al (2011) Rapid cancer detection by topically spraying a gamma-glutamyltranspeptidase-activated fluorescent probe. Sci Transl Med. 3:110ra119. https://doi.org/10.1126/scitranslmed.3002823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Nawimanage RR, Prasai B, Hettiarachchi SU, McCarley RL (2014) Rapid, photoinduced electron transfer-modulated, turn-on fluorescent probe for detection and cellular imaging of biologically significant thiols. Anal Chem 86:12266–12271. https://doi.org/10.1021/ac503441h

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Yang J, Zhu B, Yin W, Han Z, Zheng C, Wang P, Ran C (2020) Differentiating Aβ40 and Aβ42 in amyloid plaques with a small molecule fluorescence probe. Chem Sci. 11:5238–5245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Cao K, Farahi M, Dakanali M, Chang WM, Sigurdson CJ, Theodorakis EA, Yang J (2012) Aminonaphthlanene 2-cyanoacrylate (ANCA) probes fluorescently discriminate between amyloid-beta and prion plaques in brain. J Am Chem Sochttps://doi.org/10.1021/ja3063698

  85. Li Y, Cai Z, Liu S, Zhang H, Wong STH, Lam JWY, Kwok RTK, Qian J, Tang BZ (2020) Design of AIEgens for near-infrared IIb imaging through structural modulation at molecular and morphological levels. Nat Commun 11:1255. https://doi.org/10.1038/s41467-020-15095-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Zhang X, Tian Y, Li Z, Tian X, Sun H, Liu H, Moore A, Ran C (2013) Design and synthesis of curcumin analogues for in vivo fluorescence imaging and inhibiting copper-induced cross-linking of amyloid beta species in Alzheimer’s disease. J Am Chem Soc 135:16397–16409. https://doi.org/10.1021/ja405239v

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zhang X, Tian Y, Zhang C, Tian X, Ross AW, Moir RD, Sun H, Tanzi RE, Moore A, Ran C (2015) Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease. Proc Natl Acad Sci U S A 112:9734–9739. https://doi.org/10.1073/pnas.1505420112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Ediburgh. Raman Scattering in fluorescence emission spectra - common errors in fluorescence spectroscopy. 2020

  89. Jameson DM. Introduction to Fluorescence. CRC Press; 2019.

  90. Fery-Forgues S, Lavabre D (1999) Are fluorescence quantum yields so tricky to measure? A demonstration using familiar stationery products. J Chem Edu. 76:1260–1264

    Article  CAS  Google Scholar 

  91. Wurth C, Grabolle M, Pauli J, Spieles M, Resch-Genger U (2013) Relative and absolute determination of fluorescence quantum yields of transparent samples. Nat Protoc 8:1535–1550. https://doi.org/10.1038/nprot.2013.087

    Article  CAS  PubMed  Google Scholar 

  92. Berezin MY, Achilefu S (2010) Fluorescence lifetime measurements and biological imaging. Chem Rev 110:2641–2684. https://doi.org/10.1021/cr900343z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Chen H, Ahsan SS, Santiago-Berrios MB, Abruna HD, Webb WW (2010) Mechanisms of quenching of Alexa fluorophores by natural amino acids. J Am Chem Soc 132:7244–7245. https://doi.org/10.1021/ja100500k

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Kada G, Kaiser K, Falk H, Gruber HJ (1999) Rapid estimation of avidin and streptavidin by fluorescence quenching or fluorescence polarization. Biochim Biophys Acta 1427:44–48. https://doi.org/10.1016/s0304-4165(98)00177-9

    Article  CAS  PubMed  Google Scholar 

  95. Yang W, Chen X, Su H, Fang W, Zhang Y (2015) The fluorescence regulation mechanism of the paramagnetic metal in a biological HNO sensor. Chem Commun (Camb) 51:9616–9619. https://doi.org/10.1039/c5cc00787a

    Article  CAS  PubMed  Google Scholar 

  96. Deng Y, Yuan W, Jia Z, Liu G (2014) H- and J-aggregation of fluorene-based chromophores. J Phys Chem B 118:14536–14545. https://doi.org/10.1021/jp510520m

    Article  CAS  PubMed  Google Scholar 

  97. Divya O, Mishra AK (2008) Understanding the concept of concentration-dependent red-shift in synchronous fluorescence spectra: prediction of lambda(SFS)(max) and optimization of Deltalambda for synchronous fluorescence scan. Anal Chim Acta 630:47–56. https://doi.org/10.1016/j.aca.2008.09.056

    Article  CAS  PubMed  Google Scholar 

  98. Ahmed SA, Zang ZW, Yoo KM, Ali MA, Alfano RR (1994) Effect of multiple light scattering and self-absorption on the fluorescence and excitation spectra of dyes in random media. Appl Opt 33:2746–2750. https://doi.org/10.1364/AO.33.002746

    Article  CAS  PubMed  Google Scholar 

  99. Luo J, Xie Z, Lam JW, Cheng L, Chen H, Qiu C, Kwok HS, Zhan X, Liu Y, Zhu D, et al (2001) Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. Chem Commun (Camb). 1740–1741

  100. Liang J, Tang BZ, Liu B (2015) Specific light-up bioprobes based on AIEgen conjugates. Chem Soc Rev 44:2798–2811. https://doi.org/10.1039/c4cs00444b

    Article  CAS  PubMed  Google Scholar 

  101. Mei J, Leung NL, Kwok RT, Lam JW, Tang BZ (2015) Aggregation-induced emission: together we shine, united we soar! Chem Rev 115:11718–11940. https://doi.org/10.1021/acs.chemrev.5b00263

    Article  CAS  PubMed  Google Scholar 

  102. Song L, Hennink EJ, Young IT, Tanke HJ (1995) Photobleaching kinetics of fluorescein in quantitative fluorescence microscopy. Biophys J 68:2588–2600. https://doi.org/10.1016/S0006-3495(95)80442-X

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Song L, Varma CA, Verhoeven JW, Tanke HJ (1996) Influence of the triplet excited state on the photobleaching kinetics of fluorescein in microscopy. Biophys J 70:2959–2968. https://doi.org/10.1016/S0006-3495(96)79866-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Zheng Q, Jockusch S, Zhou Z, Blanchard SC (2014) The contribution of reactive oxygen species to the photobleaching of organic fluorophores. Photochem Photobiol 90:448–454. https://doi.org/10.1111/php.12204

    Article  CAS  PubMed  Google Scholar 

  105. Swaminathan R, Hoang CP, Verkman AS (1997) Photobleaching recovery and anisotropy decay of green fluorescent protein GFP-S65T in solution and cells: cytoplasmic viscosity probed by green fluorescent protein translational and rotational diffusion. Biophys J 72:1900–1907. https://doi.org/10.1016/S0006-3495(97)78835-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Sinnecker D, Voigt P, Hellwig N, Schaefer M (2005) Reversible photobleaching of enhanced green fluorescent proteins. Biochem 44:7085–7094. https://doi.org/10.1021/bi047881x

    Article  CAS  Google Scholar 

  107. Panjehshahin MR, Bowmer CJ, Yates MS (1989) A pitfall in the use of double-reciprocal plots to estimate the intrinsic molar fluorescence of ligands bound to albumin. Biochem Pharmacol 38:155–159. https://doi.org/10.1016/0006-2952(89)90162-7

    Article  CAS  PubMed  Google Scholar 

  108. Zhang X, Tian Y, Li Z, Tian X, Sun H, Liu H, Moore A, Ran C (2013) Design and synthesis of curcumin analogues for in vivo fluorescence imaging and inhibiting copper-induced cross-linking of amyloid beta species in Alzheimer’s disease. J Am Chem Soc 135:16397–16409. https://doi.org/10.1021/ja405239v

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Wijesekara N, Ahrens R, Sabale M, Wu L, Ha K, Verdile G, Fraser PE (2017) Amyloid-beta and islet amyloid pathologies link Alzheimer’s disease and type 2 diabetes in a transgenic model. FASEB J 31:5409–5418. https://doi.org/10.1096/fj.201700431R

    Article  CAS  PubMed  Google Scholar 

  110. Wang C, Schroeder FA, Wey HY, Borra R, Wagner FF, Reis S, Kim SW, Holson EB, Haggarty SJ, Hooker JM (2014) In vivo imaging of histone deacetylases (HDACs) in the central nervous system and major peripheral organs. J Med Chem 57:7999–8009. https://doi.org/10.1021/jm500872p

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Strebl MG, Wang C, Schroeder FA, Placzek MS, Wey HY, Van de Bittner GC, Neelamegam R, Hooker JM (2016) Development of a fluorinated class-I HDAC radiotracer reveals key chemical determinants of brain penetrance. ACS Chem Neurosci 7:528–533. https://doi.org/10.1021/acschemneuro.5b00297

    Article  CAS  PubMed  Google Scholar 

  112. Xing P, Niu Y, Mu R, Wang Z, Xie D, Li H, Dong L, Wang C (2020) A pocket-escaping design to prevent the common interference with near-infrared fluorescent probes in vivo. Nat Commun 11:1573. https://doi.org/10.1038/s41467-020-15323-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Gerriets T, Li F, Silva MD, Meng X, Brevard M, Sotak CH, Fisher M (2003) The macrosphere model: evaluation of a new stroke model for permanent middle cerebral artery occlusion in rats. J Neurosci Methods 122:201–211. https://doi.org/10.1016/s0165-0270(02)00322-9

    Article  PubMed  Google Scholar 

  114. Carstens E, Moberg GP (2000) Recognizing pain and distress in laboratory animals. ILAR J 41:62–71. https://doi.org/10.1093/ilar.41.2.62

    Article  CAS  PubMed  Google Scholar 

  115. Hawkins P (2002) Recognizing and assessing pain, suffering and distress in laboratory animals: a survey of current practice in the UK with recommendations. Lab Anim 36:378–395. https://doi.org/10.1258/002367702320389044

    Article  CAS  PubMed  Google Scholar 

  116. Gelderblom H, Verweij J, Nooter K, Sparreboom A (2001) Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer 37:1590–1598. https://doi.org/10.1016/s0959-8049(01)00171-x

    Article  CAS  PubMed  Google Scholar 

  117. Bodratti AM, Alexandridis P (2018) Formulation of poloxamers for drug delivery. J Funct Biomater. 9. https://doi.org/10.3390/jfb9010011

  118. Su Y, Walker JR, Park Y, Smith TP, Liu LX, Hall MP, Labanieh L, Hurst R, Wang DC, Encell LP et al (2020) Novel NanoLuc substrates enable bright two-population bioluminescence imaging in animals. Nat Methods 17:852–860. https://doi.org/10.1038/s41592-020-0889-6

    Article  CAS  PubMed  Google Scholar 

  119. Kalepu S, Nekkanti V (2015) Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharm Sin B 5:442–453. https://doi.org/10.1016/j.apsb.2015.07.003

    Article  PubMed  PubMed Central  Google Scholar 

  120. Diehl KH, Hull R, Morton D, Pfister R, Rabemampianina Y, Smith D, Vidal JM, van de Vorstenbosch C (2001) European Federation of Pharmaceutical Industries A, European Centre for the Validation of Alternative M. A good practice guide to the administration of substances and removal of blood, including routes and volumes. J Appl Toxicol. 21:15–23. https://doi.org/10.1002/jat.727

    Article  CAS  PubMed  Google Scholar 

  121. Hull RM (1995) Guideline limit volumes for dosing animals in the preclinical stage of safety evaluation. Toxicology Subcommittee of the Association of the British Pharmaceutical Industry. Hum Exp Toxicol. 14:305–307. https://doi.org/10.1177/096032719501400312

    Article  CAS  PubMed  Google Scholar 

  122. Fueger BJ, Czernin J, Hildebrandt I, Tran C, Halpern BS, Stout D, Phelps ME, Weber WA (2006) Impact of animal handling on the results of 18F-FDG PET studies in mice. J Nucl Med : Off Publ, Soc Nucl Med 47:999–1006

    CAS  Google Scholar 

  123. Ran C, Moore A (2012) Spectral unmixing imaging of wavelength-responsive fluorescent probes: an application for the real-time report of amyloid beta species in Alzheimer’s disease. Mol imag biol 14:293–300. https://doi.org/10.1007/s11307-011-0501-7

    Article  Google Scholar 

  124. Yang J, Yin W, Van R, Yin K, Wang P, Zheng C, Zhu B, Ran K, Zhang C, Kumar M et al (2020) Turn-on chemiluminescence probes and dual-amplification of signal for detection of amyloid beta species in vivo. Nat Commun 11:4052. https://doi.org/10.1038/s41467-020-17783-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Zhu B, Godavarty A (2016) Near-infrared fluorescence-enhanced optical tomography. Biomed Res Int 2016:5040814. https://doi.org/10.1155/2016/5040814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Sahu AK, Roy R, Joshi A, Sevick-Muraca EM (2005) Evaluation of anatomical structure and non-uniform distribution of imaging agent in near-infrared fluorescence-enhanced optical tomography. Opt Express 13:10182–10199. https://doi.org/10.1364/opex.13.010182

    Article  PubMed  Google Scholar 

  127. Stuker F, Ripoll J, Rudin M (2011) Fluorescence molecular tomography: principles and potential for pharmaceutical research. Pharmaceutics 3:229–274. https://doi.org/10.3390/pharmaceutics3020229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Wang K, Wang Q, Luo Q, Yang X (2015) Fluorescence molecular tomography in the second near-infrared window. Opt Express 23:12669–12679. https://doi.org/10.1364/OE.23.012669

    Article  CAS  PubMed  Google Scholar 

  129. Ray P, Gambhir SS (2007) Noninvasive imaging of molecular events with bioluminescent reporter genes in living subjects. Methods Mol Biol 411:131–144. https://doi.org/10.1007/978-1-59745-549-7_10

    Article  CAS  PubMed  Google Scholar 

  130. Hutchens M, Luker GD (2007) Applications of bioluminescence imaging to the study of infectious diseases. Cell Microbiol 9:2315–2322. https://doi.org/10.1111/j.1462-5822.2007.00995.x

    Article  CAS  PubMed  Google Scholar 

  131. Nakatsu T, Ichiyama S, Hiratake J, Saldanha A, Kobashi N, Sakata K, Kato H (2006) Structural basis for the spectral difference in luciferase bioluminescence. Nature 440:372–376. https://doi.org/10.1038/nature04542

    Article  CAS  PubMed  Google Scholar 

  132. Yao Z, Zhang BS, Prescher JA (2018) Advances in bioluminescence imaging: new probes from old recipes. Curr Opin Chem Biol 45:148–156. https://doi.org/10.1016/j.cbpa.2018.05.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Takakura H, Kojima R, Kamiya M, Kobayashi E, Komatsu T, Ueno T, Terai T, Hanaoka K, Nagano T, Urano Y (2015) New class of bioluminogenic probe based on bioluminescent enzyme-induced electron transfer: BioLeT. J Am Chem Soc 137:4010–4013. https://doi.org/10.1021/ja511014w

    Article  CAS  PubMed  Google Scholar 

  134. Xu MM, Ren WM, Tang XC, Hu YH, Zhang HY (2016) Advances in development of fluorescent probes for detecting amyloid-beta aggregates. Acta Pharmacol Sin 37:719–730. https://doi.org/10.1038/aps.2015.155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Lu L, Li B, Ding S, Fan Y, Wang S, Sun C, Zhao M, Zhao CX, Zhang F (2020) NIR-II bioluminescence for in vivo high contrast imaging and in situ ATP-mediated metastases tracing. Nat Commun 11:4192. https://doi.org/10.1038/s41467-020-18051-1

    Article  PubMed  PubMed Central  Google Scholar 

  136. Mofford DM, Reddy GR, Miller SC (2014) Aminoluciferins extend firefly luciferase bioluminescence into the near-infrared and can be preferred substrates over D-luciferin. J Am Chem Soc 136:13277–13282. https://doi.org/10.1021/ja505795s

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Jathoul AP, Grounds H, Anderson JC, Pule MA (2014) A dual-color far-red to near-infrared firefly luciferin analogue designed for multiparametric bioluminescence imaging. Angew Chem Int Ed Engl 53:13059–13063. https://doi.org/10.1002/anie.201405955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Hall MP, Woodroofe CC, Wood MG, Que I, Van’t Root M, Ridwan Y, Shi C, Kirkland TA, Encell LP, Wood KV et al (2018) Click beetle luciferase mutant and near infrared naphthyl-luciferins for improved bioluminescence imaging. Nat Commun. 9:132. https://doi.org/10.1038/s41467-017-02542-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Iwano S, Sugiyama M, Hama H, Watakabe A, Hasegawa N, Kuchimaru T, Tanaka KZ, Takahashi M, Ishida Y, Hata J et al (2018) Single-cell bioluminescence imaging of deep tissue in freely moving animals. Sci 359:935–939. https://doi.org/10.1126/science.aaq1067

    Article  CAS  Google Scholar 

  140. Ikeda Y, Nomoto T, Hiruta Y, Nishiyama N, Citterio D (2020) Ring-fused firefly luciferins: expanded palette of near-infrared emitting bioluminescent substrates. Anal Chem 92:4235–4243. https://doi.org/10.1021/acs.analchem.9b04562

    Article  CAS  PubMed  Google Scholar 

  141. Kuchimaru T, Iwano S, Kiyama M, Mitsumata S, Kadonosono T, Niwa H, Maki S, Kizaka-Kondoh S (2016) A luciferin analogue generating near-infrared bioluminescence achieves highly sensitive deep-tissue imaging. Nat Commun 7:11856. https://doi.org/10.1038/ncomms11856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Wang Y, An R, Luo Z, Ye D (2018) Firefly luciferin-inspired biocompatible chemistry for protein labeling and in vivo imaging. Chem 24:5707–5722. https://doi.org/10.1002/chem.201704349

    Article  CAS  Google Scholar 

  143. Prescher JA, Contag CH (2010) Guided by the light: visualizing biomolecular processes in living animals with bioluminescence. Curr Opin Chem Biol 14:80–89. https://doi.org/10.1016/j.cbpa.2009.11.001

    Article  CAS  PubMed  Google Scholar 

  144. England CG, Ehlerding EB, Cai W (2016) NanoLuc: a small luciferase is brightening up the field of bioluminescence. Bioconjug Chem 27:1175–1187. https://doi.org/10.1021/acs.bioconjchem.6b00112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Thorne N, Auld DS, Inglese J (2010) Apparent activity in high-throughput screening: origins of compound-dependent assay interference. Curr Opin Chem Biol 14:315–324. https://doi.org/10.1016/j.cbpa.2010.03.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Wu W, Su J, Tang C, Bai H, Ma Z, Zhang T, Yuan Z, Li Z, Zhou W, Zhang H et al (2017) cybLuc: an effective aminoluciferin derivative for deep bioluminescence imaging. Anal Chem 89:4808–4816. https://doi.org/10.1021/acs.analchem.6b03510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Saito-Moriya R, Nakayama J, Kamiya G, Kitada N, Obata R, Maki SA, Aoyama H (2021) How to select firefly luciferin analogues for in vivo imaging. Int J Mol Sci. 22. https://doi.org/10.3390/ijms22041848

  148. Hall MP, Unch J, Binkowski BF, Valley MP, Butler BL, Wood MG, Otto P, Zimmerman K, Vidugiris G, Machleidt T et al (2012) Engineered luciferase reporter from a deep sea shrimp utilizing a novel imidazopyrazinone substrate. ACS Chem Biol 7:1848–1857. https://doi.org/10.1021/cb3002478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Fleiss A, Sarkisyan KS (2019) A brief review of bioluminescent systems (2019). Curr Genet 65:877–882. https://doi.org/10.1007/s00294-019-00951-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Kuo C, Coquoz O, Troy TL, Xu H, Rice BW (2007) Three-dimensional reconstruction of in vivo bioluminescent sources based on multispectral imaging. J Biomed Opt 12:024007. https://doi.org/10.1117/1.2717898

    Article  CAS  PubMed  Google Scholar 

  151. Hananya N, Shabat D (2019) Recent Advances and Challenges in Luminescent Imaging: Bright Outlook for Chemiluminescence of Dioxetanes in Water. ACS Cent Sci 5:949–959. https://doi.org/10.1021/acscentsci.9b00372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Yang M, Huang J, Fan J, Du J, Pu K, Peng X (2020) Chemiluminescence for bioimaging and therapeutics: recent advances and challenges. Chem Soc Rev 49:6800–6815. https://doi.org/10.1039/d0cs00348d

    Article  CAS  PubMed  Google Scholar 

  153. Jiang Y, Huang J, Zhen X, Zeng Z, Li J, Xie C, Miao Q, Chen J, Chen P, Pu K (2019) A generic approach towards afterglow luminescent nanoparticles for ultrasensitive in vivo imaging. Nat Commun 10:2064. https://doi.org/10.1038/s41467-019-10119-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Isobe H, Yamanaka S, Kuramitsu S, Yamaguchi K (2008) Regulation mechanism of spin-orbit coupling in charge-transfer-induced luminescence of imidazopyrazinone derivatives. J Am Chem Soc 130:132–149. https://doi.org/10.1021/ja073834r

    Article  CAS  PubMed  Google Scholar 

  155. Barondeau DP, Putnam CD, Kassmann CJ, Tainer JA, Getzoff ED (2003) Mechanism and energetics of green fluorescent protein chromophore synthesis revealed by trapped intermediate structures. Proc Natl Acad Sci U S A 100:12111–12116. https://doi.org/10.1073/pnas.2133463100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Lambrechts D, Roeffaers M, Goossens K, Hofkens J, Vande Velde G, Van de Putte T, Schrooten J, Van Oosterwyck H (2014) A causal relation between bioluminescence and oxygen to quantify the cell niche. PLoS One. 9:e97572. https://doi.org/10.1371/journal.pone.0097572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Liu Y, Zhao YM, Akers W, Tang ZY, Fan J, Sun HC, Ye QH, Wang L, Achilefu S (2013) First in-human intraoperative imaging of HCC using the fluorescence goggle system and transarterial delivery of near-infrared fluorescent imaging agent: a pilot study. Transl Res 162:324–331. https://doi.org/10.1016/j.trsl.2013.05.002

    Article  PubMed  PubMed Central  Google Scholar 

  158. Okusanya OT, Holt D, Heitjan D, Deshpande C, Venegas O, Jiang J, Judy R, DeJesus E, Madajewski B, Oh K et al (2014) Intraoperative near-infrared imaging can identify pulmonary nodules. Ann Thorac Surg 98:1223–1230. https://doi.org/10.1016/j.athoracsur.2014.05.026

    Article  PubMed  PubMed Central  Google Scholar 

  159. Teng CW, Cho SS, Singh Y, De Ravin E, Somers K, Buch L, Brem S, Singhal S, Delikatny EJ, Lee JYK (2021) Second window ICG predicts gross-total resection and progression-free survival during brain metastasis surgery. J Neurosurg. 1–10. https://doi.org/10.3171/2020.8.JNS201810

  160. Mahalingam SM, Kularatne SA, Myers CH, Gagare P, Norshi M, Liu X, Singhal S, Low PS (2018) Evaluation of novel tumor-targeted near-infrared probe for fluorescence-guided surgery of cancer. J Med Chem 61:9637–9646. https://doi.org/10.1021/acs.jmedchem.8b01115

    Article  CAS  PubMed  Google Scholar 

  161. Harmsen S, Teraphongphom N, Tweedle MF, Basilion JP, Rosenthal EL (2017) Optical surgical navigation for precision in tumor resections. Mol Imaging Biol 19:357–362. https://doi.org/10.1007/s11307-017-1054-1

    Article  PubMed  PubMed Central  Google Scholar 

  162. Gao RW, Teraphongphom N, de Boer E, van den Berg NS, Divi V, Kaplan MJ, Oberhelman NJ, Hong SS, Capes E, Colevas AD et al (2018) Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers. Theranostics 8:2488–2495. https://doi.org/10.7150/thno.24487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Ter Weele EJ, Terwisscha van Scheltinga AG, Linssen MD, Nagengast WB, Lindner I, Jorritsma-Smit A, de Vries EG, Kosterink JG, Lub-de Hooge MN (2016) Development, preclinical safety, formulation, and stability of clinical grade bevacizumab-800CW, a new near infrared fluorescent imaging agent for first in human use. Eur J Pharm Biopharm. 104:226–234. https://doi.org/10.1016/j.ejpb.2016.05.008

    Article  CAS  PubMed  Google Scholar 

  164. Figueiredo JL, Alencar H, Weissleder R, Mahmood U (2006) Near infrared thoracoscopy of tumoral protease activity for improved detection of peripheral lung cancer. Int J Cancer 118:2672–2677. https://doi.org/10.1002/ijc.21713

    Article  CAS  PubMed  Google Scholar 

  165. Liu Y, Walker E, Iyer SR, Biro M, Kim I, Zhou B, Straight B, Bogyo M, Basilion JP, Popkin DL et al (2019) Molecular imaging and validation of margins in surgically excised nonmelanoma skin cancer specimens. J Med Imaging (Bellingham). 6:016001. https://doi.org/10.1117/1.JMI.6.1.016001

    Article  PubMed  Google Scholar 

  166. Hadjipanayis CG, Widhalm G, Stummer W (2015) What is the surgical benefit of utilizing 5-aminolevulinic acid for fluorescence-guided surgery of malignant gliomas? Neurosurg 77:663–673. https://doi.org/10.1227/NEU.0000000000000929

    Article  Google Scholar 

  167. Lane PM, Gilhuly T, Whitehead P, Zeng H, Poh CF, Ng S, Williams PM, Zhang L, Rosin MP, MacAulay CE (2006) Simple device for the direct visualization of oral-cavity tissue fluorescence. J Biomed Opt. 11:024006. https://doi.org/10.1117/1.2193157

    Article  PubMed  Google Scholar 

  168. Poh CF, Anderson DW, Durham JS, Chen J, Berean KW, MacAulay CE, Rosin MP (2016) Fluorescence visualization-guided surgery for early-stage oral cancer. JAMA Otolaryngol Head Neck Surg 142:209–216. https://doi.org/10.1001/jamaoto.2015.3211

    Article  PubMed  Google Scholar 

  169. Mondal SB, Gao S, Zhu N, Liang R, Gruev V, Achilefu S (2014) Real-time fluorescence image-guided oncologic surgery. Adv Cancer Res 124:171–211. https://doi.org/10.1016/B978-0-12-411638-2.00005-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Zaric B, Becker HD, Perin B, Stojanovic G, Jovelic A, Eri Z, Panjkovic M, Ilic MD, Matijasevic J, Antonic M (2010) Autofluorescence imaging videobronchoscopy improves assessment of tumor margins and affects therapeutic strategy in central lung cancer. Jpn J Clin Oncol 40:139–145. https://doi.org/10.1093/jjco/hyp135

    Article  PubMed  Google Scholar 

  171. Mondal SB, O’Brien CM, Bishop K, Fields RC, Margenthaler JA, Achilefu S (2020) Repurposing molecular imaging and sensing for cancer image-guided surgery. J Nucl Med 61:1113–1122. https://doi.org/10.2967/jnumed.118.220426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Randall LM, Wenham RM, Low PS, Dowdy SC, Tanyi JL (2019) A phase II, multicenter, open-label trial of OTL38 injection for the intra-operative imaging of folate receptor-alpha positive ovarian cancer. Gynecol Oncol 155:63–68. https://doi.org/10.1016/j.ygyno.2019.07.010

    Article  CAS  PubMed  Google Scholar 

  173. Tanyi JL, Chon HS, Morgan MA, Chambers SK, Han ES, Butler KA, Langstraat CL, Powell MA, Randall LM, Vahrmeijer AL et al (2021) Phase 3, randomized, single-dose, open-label study to investigate the safety and efficacy of pafolacianine sodium injection (OTL38) for intraoperative imaging of folate receptor positive ovarian cancer. J Clin Oncol 39:5503–5503. https://doi.org/10.1200/JCO.2021.39.15_suppl.5503

    Article  Google Scholar 

  174. Azari F, Kennedy G, Bernstein E, Hadjipanayis C, Vahrmeijer A, Smith B, Rosenthal E, Sumer B, Tian J, Henderson E, Intraoperative molecular imaging clinical trials: a review of, et al (2020) conference proceedings. J Biomed Opt 2021:26. https://doi.org/10.1117/1.Jbo.26.5.050901

    Article  Google Scholar 

  175. O’Shannessy DJ, Somers EB, Wang LC, Wang H, Hsu R (2015) Expression of folate receptors alpha and beta in normal and cancerous gynecologic tissues: correlation of expression of the beta isoform with macrophage markers. J Ovarian Res 8:29. https://doi.org/10.1186/s13048-015-0156-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Shen J, Hu Y, Putt KS, Singhal S, Han H, Visscher DW, Murphy LM, Low PS (2018) Assessment of folate receptor alpha and beta expression in selection of lung and pancreatic cancer patients for receptor targeted therapies. Oncotarget 9:4485–4495. https://doi.org/10.18632/oncotarget.23321

    Article  PubMed  Google Scholar 

  177. Tipirneni KE, Warram JM, Moore LS, Prince AC, de Boer E, Jani AH, Wapnir IL, Liao JC, Bouvet M, Behnke NK et al (2017) Oncologic procedures amenable to fluorescence-guided surgery. Ann Surg 266:36–47. https://doi.org/10.1097/sla.0000000000002127

    Article  PubMed  Google Scholar 

  178. Robertson R, Germanos MS, Li C, Mitchell GS, Cherry SR, Silva MD (2009) Optical imaging of Cerenkov light generation from positron-emitting radiotracers. Phys Med Biol 54:N355-365. https://doi.org/10.1088/0031-9155/54/16/N01

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Liu H, Zhang X, Xing B, Han P, Gambhir SS, Cheng Z (2010) Radiation-luminescence-excited quantum dots for in vivo multiplexed optical imaging. Small 6:1087–1091. https://doi.org/10.1002/smll.200902408

    Article  CAS  PubMed  Google Scholar 

  180. Dothager RS, Goiffon RJ, Jackson E, Harpstrite S, Piwnica-Worms D (2010) Cerenkov radiation energy transfer (CRET) imaging: a novel method for optical imaging of PET isotopes in biological systems. PLoS One. 5:e13300. https://doi.org/10.1371/journal.pone.0013300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Li C, Mitchell GS, Cherry SR (2010) Cerenkov luminescence tomography for small-animal imaging. Opt Lett 35:1109–1111. https://doi.org/10.1364/OL.35.001109

    Article  PubMed  PubMed Central  Google Scholar 

  182. Ruggiero A, Holland JP, Lewis JS, Grimm J (2010) Cerenkov luminescence imaging of medical isotopes. J Nucl Med : Off Publ, Soc Nucl Med 51:1123–1130. https://doi.org/10.2967/jnumed.110.076521

    Article  CAS  Google Scholar 

  183. Spinelli AE, D’Ambrosio D, Calderan L, Marengo M, Sbarbati A, Boschi F (2010) Cerenkov radiation allows in vivo optical imaging of positron emitting radiotracers. Phys Med Biol 55:483–495. https://doi.org/10.1088/0031-9155/55/2/010

    Article  PubMed  Google Scholar 

  184. Hu Z, Liang J, Yang W, Fan W, Li C, Ma X, Chen X, Li X, Qu X, Wang J et al (2010) Experimental Cerenkov luminescence tomography of the mouse model with SPECT imaging validation. Opt Express 18:24441–24450. https://doi.org/10.1364/OE.18.024441

    Article  CAS  PubMed  Google Scholar 

  185. Lewis MA, Kodibagkar VD, Oz OK, Mason RP (2010) On the potential for molecular imaging with Cerenkov luminescence. Opt Lett 35:3889–3891. https://doi.org/10.1364/OL.35.003889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Arroyo AD, Guzman AE, Kachur AV, Saylor SJ, Popov AV, Delikatny EJ (2019) Development of fluorinated naphthofluoresceins for Cerenkov imaging. J Fluor Chem 225:27–34. https://doi.org/10.1016/j.jfluchem.2019.05.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Czupryna J, Kachur AV, Blankemeyer E, Popov AV, Arroyo AD, Karp JS, Delikatny EJ (2015) Cerenkov-specific contrast agents for detection of pH in vivo. J Nucl Med 56:483–488. https://doi.org/10.2967/jnumed.114.146605

    Article  CAS  PubMed  Google Scholar 

  188. Liu H, Ren G, Miao Z, Zhang X, Tang X, Han P, Gambhir SS, Cheng Z (2010) Molecular optical imaging with radioactive probes. PLoS One. 5:e9470. https://doi.org/10.1371/journal.pone.0009470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Shaffer TM, Pratt EC, Grimm J (2017) Utilizing the power of Cerenkov light with nanotechnology. Nat Nanotechnol 12:106–117. https://doi.org/10.1038/nnano.2016.301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Ran C, Zhang Z, Hooker J, Moore A (2012) In vivo photoactivation without “light”: use of Cherenkov radiation to overcome the penetration limit of light. Mol Imaging Biol 14:156–162. https://doi.org/10.1007/s11307-011-0489-z

    Article  PubMed  Google Scholar 

  191. Zhang X, Kuo C, Moore A, Ran C (2013) In vivo optical imaging of interscapular brown adipose tissue with 18F-FDG via Cerenkov luminescence imaging. PLoS One. 8:e62007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Thorek D, Robertson R, Bacchus WA, Hahn J, Rothberg J, Beattie BJ, Grimm J (2012) Cerenkov imaging - a new modality for molecular imaging. Am J Nucl Med Mol Imaging. 2:163–173

    PubMed  PubMed Central  Google Scholar 

  193. Ruggiero A, Holland JP, Lewis JS, Grimm J (2010) Cerenkov luminescence imaging of medical isotopes. J Nucl Med 51:1123–1130. https://doi.org/10.2967/jnumed.110.076521

    Article  CAS  PubMed  Google Scholar 

  194. Carpenter CM, Ma X, Liu H, Sun C, Pratx G, Wang J, Gambhir SS, Xing L, Cheng Z (2014) Cerenkov luminescence endoscopy: improved molecular sensitivity with beta–emitting radiotracers. J Nucl Med 55:1905–1909. https://doi.org/10.2967/jnumed.114.139105

    Article  PubMed  Google Scholar 

  195. olde Heuvel J, de Wit-van der Veen BL, Vyas KN, Tuch DS, Grootendorst MR, Stokkel MPM, Slump CH (2019) Performance evaluation of Cerenkov luminescence imaging: a comparison of 68Ga with 18F. EJNMMI Physics 6:17. https://doi.org/10.1186/s40658-019-0255-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Mitchell GS, Lloyd PNT, Cherry SR (2020) Cerenkov luminescence and PET imaging of 90Y: capabilities and limitations in small animal applications. Phys Med Biol 65:065006. https://doi.org/10.1088/1361-6560/ab7502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  197. Thorek DL, Ogirala A, Beattie BJ, Grimm J (2013) Quantitative imaging of disease signatures through radioactive decay signal conversion. Nat Med 19:1345–1350. https://doi.org/10.1038/nm.3323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Arroyo AD, Guzman AE, Kachur AV, Popov AV, Delikatny EJ (2021) Development of 18F-labeled resazurin derivatives for the detection of tumor metabolic activity using Cerenkov imaging. Frontiers in Physics. 9. https://doi.org/10.3389/fphy.2021.652179

  199. Thorek DL, Riedl CC, Grimm J (2014) Clinical Cerenkov luminescence imaging of (18)F-FDG. J Nucl Med 55:95–98. https://doi.org/10.2967/jnumed.113.127266

    Article  CAS  PubMed  Google Scholar 

  200. Spinelli AE, Schiariti MP, Grana CM, Ferrari M, Cremonesi M, Boschi F (2016) Cerenkov and radioluminescence imaging of brain tumor specimens during neurosurgery. J Biomed Opt 21:50502. https://doi.org/10.1117/1.JBO.21.5.050502

    Article  PubMed  Google Scholar 

  201. Darr C, Harke NN, Radtke JP, Yirga L, Kesch C, Grootendorst MR, Fendler WP, Costa PF, Rischpler C, Praus C et al (2020) Intraoperative (68)Ga-PSMA Cerenkov luminescence imaging for surgical margins in radical prostatectomy: a feasibility study. J Nucl Med 61:1500–1506. https://doi.org/10.2967/jnumed.119.240424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Bagguley D, Cumberbatch M, Lawrentschuk N, Murphy DG (2020) Cerenkov luminescence imaging for surgical margins in radical prostatectomy: a surgical perspective. J Nucl Med 61:1498–1499. https://doi.org/10.2967/jnumed.120.243303

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank members of the WMIS education committee (2019–2022) for their tremendous support for the organizing of the writing of this white paper. We also thanks Lisa Baird for her administrative efforts on behalf of WMIS. This work was partially supported by R21AG059134, R56AG059814, S10OD028609, and R01AG055413 awards from NIA (CR), and R01CA226412, R01CA266234, 1 P01CA254859 awards from NCI (EJD).

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Authors and Affiliations

  1. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Room 2301, Building 149, Charlestown, Boston, MA, 02129, USA

    Chongzhao Ran

  2. Visiopharm A/S, Agern Alle 24, 2970, Hørsholm, Denmark

    James R. Mansfield

  3. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Mingfeng Bai

  4. Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, 48201, USA

    Nerissa T. Viola

  5. Department of Radiology, The Clatterbridge Cancer Centre NHS Foundation Trust, Pembroke Place, Liverpool, L7 8YA, UK

    Abhishek Mahajan

  6. Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    E. James Delikatny

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Correspondence to Chongzhao Ran, James R. Mansfield or E. James Delikatny.

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Ran, C., Mansfield, J.R., Bai, M. et al. Practical Guidance for Developing Small-Molecule Optical Probes for In Vivo Imaging. Mol Imaging Biol 25, 240–264 (2023). https://doi.org/10.1007/s11307-023-01800-1

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