Introduction
Methods
Search strategy
PubMed search accessed on 03–21–2016 | Embase search accessed on 03–21–2016 |
---|---|
((“Fluorescent Dyes”[Mesh] OR pigments [Title/Abstract] OR pigment [Title/Abstract] OR stains [Title/Abstract] OR stain [Title/Abstract] OR fluorophores [Title/Abstract] OR fluorophore [Title/Abstract] OR contrast agents [Title/Abstract] OR contrast agent [Title/Abstract] OR dye [Title/Abstract] OR fluorescent [Title/Abstract] OR fluorescence [Title/Abstract] OR fluorochromes [Title/Abstract] OR fluorogenic substrate [Title/Abstract] OR coloring agents [Title/Abstract] OR coloring agent [Title/Abstract] OR luminescent agents [Title/Abstract] OR luminescent agent [Title/Abstract] OR 5-ALA [Title/Abstract] OR 5-aminolevulinic acid [Title/Abstract]) AND (“Glioma”[Mesh] OR glioma [Title/Abstract] OR gliomas [Title/Abstract] OR GBM [Title/Abstract] OR glioblastoma [Title/Abstract] OR brain tumor [Title/Abstract] OR brain tumors [Title/Abstract] OR brain tumour [Title/Abstract] OR brain tumours [Title/Abstract] OR brain cancer [Title/Abstract]) AND (“Neurosurgical Procedures”[Mesh] OR operation [Title/Abstract] OR surgery [Title/Abstract] OR surgical [Title/Abstract] OR neurosurgery [Title/Abstract] OR resection [Title/Abstract])) | (‘fluorescent dye’/exp OR pigments:ti:ab OR pigment:ti:ab OR stains:ti:ab OR stain:ti:ab OR fluorophores:ti:ab OR fluorophore:ti:ab OR (contrast AND agents):ti:ab OR (contrast AND agent):ti:ab OR dye:ti:ab OR fluorescent:ti:ab OR fluorescence:ti:ab OR fluorochromes:ti:ab OR (fluorogenic AND substrate):ti:ab OR (coloring AND agents):ti:ab OR (coloring AND agent):ti:ab OR (luminescent AND agents):ti:ab OR (luminescent AND agent):ti:ab OR 5-ALA:ti:ab OR (5-aminolevulinic AND acid):ti:ab) AND (‘glioma’/exp OR glioma:ti:ab OR gliomas:ti:ab OR GBM:ti:ab OR glioblastoma:ti:ab OR (brain AND tumor):ti:ab OR (brain AND tumors):ti:ab OR (brain AND tumour):ti:ab OR (brain AND tumours):ti:ab OR (brain AND cancer):ti:ab) AND (‘neurosurgery’/exp OR operation:ti:ab OR surgery:ti:ab OR surgical:ti:ab OR neurosurgery:ti:ab OR resection:ti:ab) |
Data extraction
Results
Year | Fluorescent agent | Study design | No. of cases | Tumor grade of patients | Control group | GTR rate (%) | TNR | Median survival (mo) | PFS (mo) | 6-PFS (%) |
---|---|---|---|---|---|---|---|---|---|---|
Stummer et al. 2000 [98] | 5-ALA | Case series | 52 | GBM | No | 63 | – | 3 | – | – |
Stummer er al. 2006 [99] | 5-ALA | RCT | 322 | HGG | Yes | 65 | – | 15 | 5 | 41 |
Eljamel et al. 2008 [26] | 5-ALA | RCT | 27 | GBM | No | – | – | 12 | 9 | – |
Hefti et al. 2008 [41] | 5-ALA | Case series | 74 | HGG | No | – | – | – | – | – |
Nabavi et al. 2009 [66] | 5-ALA | Case series | 36 | HGG | No | – | – | – | – | – |
Feigl et al. 2010 [31] | 5-ALA | Case series | 18 | HGG | No | 64 | – | – | – | 83 |
Ewelt et al. 2011 [28] | 5-ALA | Case series | 17 | HGG | No | – | – | – | – | – |
Ewelt et al. 2011 [28] | 5-ALA | Case series | 13 | LGG | No | – | – | – | – | – |
Floeth et al. 2011 [33] | 5-ALA | Case series | 21 | HGG | No | – | – | – | – | – |
Floeth et al. 2011 [33] | 5-ALA | Case series | 17 | LGG | No | – | – | – | – | – |
Diez Valle et al. 2011 [25] | 5-ALA | Case series | 28 | GBM | No | 83 | – | 16 | – | 68 |
Roberts et al. 2011 [81] | 5-ALA | Case series | 11 | GBM | No | – | – | – | – | – |
Stummer et al. 2011b [97] | 5-ALA | Case series | 243 | HGG | No | – | – | 16 | – | – |
Stummer et al. 2011a [101] | 5-ALA | RCT | 349 | HGG | Yes | – | – | 14 | – | 46 |
Idoate et al. 2011 [44] | 5-ALA | Case series | 30 | GBM | No | 83 | – | – | – | – |
Sanai et al. 2011 [84] | 5-ALA | Case series | 10 | LGG | No | – | – | – | – | – |
Valdes et al. 2011 [110] | 5-ALA | Cohort | 14 | LGG&HGG | Yes | – | – | – | – | – |
Panciani et al. 2012 [74] | 5-ALA | Case series | 23 | GBM | No | – | – | – | – | – |
Cortnum et al. 2012 [16] | 5-ALA | Case series | 13 | HGG | No | 70 | – | – | – | – |
Eyopuglu et al. 2012 [30] | 5-ALA | Case series | 37 | HGG | No | 71–100 | – | – | – | – |
Schucht et al. 2013 [87] | 5-ALA | Case series | 56 | GBM | No | 89b
| – | – | – | – |
Widhalm et al. 2013 [113] | 5-ALA | Case series | 59 | LGG&HGG | No | – | – | – | – | – |
Della puppa et al. 2013 [22] | 5-ALA | Case series | 31 | HGG | No | 74 | – | – | – | – |
Slotty et al. 2013 [94] | 5-ALA | Cohort | 253 | GBM | Yes | 49 | – | 20 | – | – |
Aldave et al. 2013 [3] | 5-ALA | Case series | 118 | HGG | No | 62 | – | 21 | – | – |
Diez Valle et al. 2014 [24] | 5-ALA | Cohort | 251 | HGG | Yes | 67 | – | – | – | 69 |
Roder et al. 2014 [82] | 5-ALA | Cohort | 66 | GBM | Yes | 46 | – | – | – | – |
Belloch et al. 2014 [6] | 5-ALA | Case series | 21 | HGG | No | 71b
| – | – | – | – |
Schucht et al. 2014 [89] | 5-ALA | Case series | 72 | GBM | No | 73 | – | – | – | – |
Coburger et al. 2014 [13] | 5-ALA | Case series | 34 | HGG | No | – | – | – | – | – |
Piquer et al. 2014 [75] | 5-ALA | Case series | 38 | HGG | No | 61 | – | – | – | – |
Stummer et al. 2014 [100] | 5-ALA | Case series | 33 | HGG | No | – | – | – | – | – |
Barbagallo et al. 2015 [5] | 5-ALA | Cohort | 50 | HGG | Yes | 97 | – | – | – | – |
Coburger et al. 2015 [14] | 5-ALA | Cohort | 33 | GBM | Yes | 100 | – | 18 | 6 | – |
Cordova et al. 2015 [15] | 5-ALA | Case series | 30 | GBM | No | – | – | – | – | 29 |
Gessler et al. 2015 [34] | 5-ALA | Case series | 32 | GBM | No | 97 | – | 19 | 14 | – |
Haj-Josseini et al. 2015 [37] | 5-ALA | Case series | 30 | HGG | No | – | – | – | – | – |
Hickmann et al. 2015 [42] | 5-ALA | Cohort | 58 | HGG | Yes | 57c
| – | 20 | 12 | – |
Noell et al. 2015 [70] | 5-ALA | Case series | 29 | HGG | No | 25 | – | 19 | – | 47 |
Schatlo et al. 2015 [85] | 5-ALA | Case series | 200 | HGG | No | – | – | – | – | – |
Szmuda et al. 2015 [105] | 5-ALA | Case series | 21 | HGG | No | 57c
| – | – | – | – |
Valdes et al. 2015 [109] | 5-ALA | Case series | 12 | LGG | No | – | – | – | – | – |
Yamada et al. 2015 [115] | 5-ALA | Case series | 99 | HGG | No | – | – | – | – | – |
Hauser et al. 2016 [40] | 5-ALA | Case series | 13 | GBM | No | 77 | – | 14 | – | 31 |
Quick-Weller et al. 2016 [78] | 5-ALA | Case series | 7 | GBM | No | – | – | – | – | – |
Teixidor et al. 2016 [106] | 5-ALA | Case series | 85 | HGG | No | 54b
| – | 14 | 7 | 58 |
Moore et al. 1948 [65] | Fluorescein | Case series | 12 | LGG&HGG | No | – | – | – | – | – |
Shinoda et al. 2003 [92] | Fluorescein | Cohort | 32 | GBM | Yes | 84b
| – | 15 | – | – |
Koc et al. 2008 [52] | Fluorescein | Cohort | 37 | GBM | Yes | 83 | – | 11 | – | – |
Chen et al. 2012 [11] | Fluorescein | Cohort | 22 | LGG&HGG | Yes | 80b
| – | – | 7 | – |
Kuroiwa et al. 1998 [54] | Fluorescein | Case series | 10 | HGG | No | 100 | – | – | – | – |
Okuda et al. 2012 [71] | Fluorescein | Case series | 10 | GBM | No | 100 | – | – | – | – |
Schebesch et al. 2013 [86] | Fluorescein | Case series | 35 | LGG&HGG | No | 80 | – | – | – | – |
Acerbi et al. 2014 [1] | Fluorescein | Case series | 20 | HGG | No | 80 | – | – | – | 72 |
Diaz et al. 2015 [23] | Fluorescein | Case series | 12 | HGG | No | 100 | – | – | – | – |
Hamancioglu et al. 2016 [38] | Fluorescein | Case series | 28 | HGG | No | 79b
| – | – | – | – |
Martirosyan et al. 2016 [64] | Fluorescein | Case series | 74 | LGG&HGG | No | – | – | – | – | – |
Hansen et al. 1993 [39] | ICG | Preclinical | – | – | No | – | – | – | – | – |
Haglund et al. 1994 [36] | ICG | Preclinical | 22 | – | No | – | – | – | – | – |
Haglund et al. 1996 [35] | ICG | Case series | 9 | LGG&HGG | No | – | – | – | – | – |
Martirosyan et al. 2011 [63] | ICG | Preclinical | 30 | – | No | – | – | – | – | – |
Eyupoglu et al. 2015 [29] | ICG | Case series | 3 | HGG | No | – | – | – | – | – |
Kremer et al. 2009 [53] | AFL-HSA | Case series | 13 | HGG | No | 69 | – | – | – | – |
Noell et al. 2011 [70] | Hypericin | Preclinical | 16 | – | No | – | 19.8 | – | – | – |
Ritz et al. 2012 [80] | Hypericin | Case series | 5 | HGG | No | – | – | – | – | – |
Lin et al. 2001 [58] | Endogenous | Case series | 26 | LGG&HGG | No | – | – | – | – | – |
Toms et al. 2005 [107] | Endogenous | Case series | 24 | LGG&HGG | No | – | – | – | – | – |
Marcu et al. 2004 [62] | Endogenous | Preclinical | 6 | – | No | – | – | – | – | – |
Yong et al. 2006 [117] | Endogenous | Case series | 31 | LGG&HGG | No | – | – | – | – | – |
Butte et al. 2011 [9] | Endogenous | Case series | 24 | LGG&HGG | No | – | – | – | – | – |
Leppert et al. 2006 [56] | Endogenous | Preclinical | – | – | No | – | – | – | – | – |
Kantelhardt et al. 2009 [50] | Endogenous | Preclinical | – | – | No | – | – | – | – | – |
Riemann et al. 2012 [79] | Endogenous | Preclinical | – | – | No | – | – | – | – | – |
Kantelhardt et al. 2016 [49] | Endogenous | Case series | 8 | – | No | – | – | – | – | – |
Veiseh et al. 2007 [111] | Fluorophore | Preclinical | 22 | – | No | – | – | – | – | – |
Lanzardo et al. 2011 [55] | Fluorophore | Preclinical | 4 | – | No | – | – | – | – | – |
Yan et al. 2011 [116] | Fluorophore | Preclinical | – | – | No | – | 1.6 | – | – | – |
Agnes et al. 2012 [2] | Fluorophore | Preclinical | – | – | No | – | – | – | – | – |
Cutter et al. 2012 [20] | Fluorophore | Preclinical | 3 | – | No | – | – | – | – | – |
Huang et al. 2012 [43] | Fluorophore | Preclinical | – | – | No | – | 16.3–79.7 | – | – | – |
Burden-Gulley et al. 2013 [7] | Fluorophore | Preclinical | – | – | No | – | 11.7–19.8 | – | – | – |
Ma et al. 2014 [61] | Fluorophore | Preclinical | – | – | No | – | – | – | – | – |
Crisp et al. 2014 [18] | Fluorophore | Preclinical | 14 | – | No | – | 7.8 | – | – | – |
Fenton et al. 2014 [32] | Fluorophore | Preclinical | 20 | – | No | – | – | – | – | – |
Butte et al. 2014 [8] | Fluorophore | Preclinical | – | – | No | – | – | – | – | – |
Qiu et al. 2015 [77] | Fluorophore | Preclinical | 36 | – | No | – | – | – | – | – |
Swanson et al. 2015 [104] | Fluorophore | Preclinical | 35 | – | Yes | – | 9.28 | – | – | – |
Warram et al. 2015 [112] | Fluorophore | Preclinical | 5 | – | No | – | – | – | – | – |
Antaris et al. 2016 [4] | Fluorophore | Preclinical | 5 | – | No | – | 5.50 | – | – | – |
Davis et al. 2010 [21] | Fluorophore | Preclinical | 15 | – | No | – | – | – | – | – |
Sexton et al. 2013 [91] | Fluorophore | Preclinical | 4 | – | No | – | – | – | – | – |
Irwin et al. 2014 [45] | Fluorophore | Preclinical | 8 | – | No | – | – | – | – | – |
Kantelhardt et al. 2010 [48] | Nanoparticle | Preclinical | 2 | – | No | – | 200–1000 | – | – | – |
Seekell et al. 2013 [90] | Nanoparticle | Preclinical | 6 | – | No | – | – | – | – | – |
Kircher et al. 2003 [51] | Nanoparticle | Preclinical | 5 | – | No | – | – | – | – | – |
Trehin et al. 2006 [108] | Nanoparticle | Preclinical | 14 | – | No | – | – | – | – | – |
Cai et al. 2006 [10] | Nanoparticle | Preclinical | – | – | Yes | – | – | – | – | – |
Jackson et al. 2007 [46] | Nanoparticle | Preclinical | – | – | No | – | – | – | – | – |
Orringer et al. 2009 [73] | Nanoparticle | Preclinical | – | – | No | – | – | – | – | – |
Jiang et al. 2013 [47] | Nanoparticle | Preclinical | 18 | – | Yes | – | – | – | – | – |
Ni et al. 2014 [68] | Nanoparticle | Preclinical | – | – | No | – | – | – | – | – |
Zhou et al. 2015 [120] | Nanoparticle | Preclinical | 6 | – | Yes | – | – | – | – | – |
Cui et al. 2015 [19] | Nanoparticle | Preclinical | 344 | – | No | – | – | – | – | – |
Roller et al. 2015 [83] | Nanoparticle | Preclinical | 10 | – | No | – | – | – | – | – |
Zhao et al. 2013 [119] | 5-ALA | Meta-analysis | 10a
| – | – | – | – | – | – | – |
Su et al.2014 [103] | Multiple | Meta-analysis | 12a
| – | – | 72 | – | – | 5 | – |
Eljamel et al. 2015 [27] | 5-ALA | Meta-analysis | 20a
| – | – | 75 | – | – | 8 | – |
Clinically tested fluorescent agents
5-aminolevulinic acid (5-ALA)
Fluorescein
Indocyanine green (ICG)
5-aminoflurescein human serum albumin
Hypericin
Endogenous fluorophores
Pre-clinically tested fluorescent agents
Molecular fluorophores
Nanoparticles
Anti-EGFR or anti-EGF
Discussion
Agent | Excitation (nm) | Emission (nm) | Mode of targeting | GTR (%) | Survival (months/%) | Adverse effects | Remark |
---|---|---|---|---|---|---|---|
5-ALA | 375–440 | 640–710 | Metabolic | 65 vs. 35a
| - 12–15 vs. 6–14a
- PFS: 5–9 vs. 4–5a
- 6-PFS: 41–46% vs. 21–28%a
| - Phototoxicity, higher rate of deterioration at 48 h | Applicable with confocal microscopy and PDT |
Fluorescein | 460–500 | 540–690 | Passive | 80–100 vs. 30– 55 | - 11–15 vs. 10–13 - PFS: 7.4 vs. 5.4 | - Coloring of skin, mucosa, and urine - Anaphylactic reactions | Applicable with confocal microscopy |
ICG | 778 | 700–850 | Passive | – | – | Anaphylactic reactions | Applicable with confocal microscopy |
Hypericin | 415–495 | 590–650 | Passive | – | – | No side effects observed | Application with PDT |
AFL-HSA | 495 | 535 | Passive | 69 | – | No side effects observed | – |
Endogenous (spectroscopy) | 337 | 360–750 | Endogenous | – | – | No side effects observed | – |
Endogenous (multiphoton tomography) | 700–1000 | Dependent on excitation intensity | Endogenous | – | – | – | Destruction of single cell in 3D matrix (rat study) |
Agent | Fluorescent compound | Emission peak (nm) | Mode of targeting | Histological accuracy |
---|---|---|---|---|
IRDye 800CW-RGD | Fluorophore | 794 | Molecular | TNR 16.3–79.7 |
Cy3-AS1411-TGN | Fluorophore | 570 | Molecular | – |
Cy5-SBK2 | Fluorophore | 670 | Molecular | TNR 11.7–19.8 |
Cyclic-RGD-PLGC (Me)AG-ACPP | Fluorophore | 670 | Molecular | TNR 7.8 |
Anti-TRP-2-Alexa fluor 488 or 750 | Fluorophore | 519 or 775 | Molecular | – |
CLR1502 | Fluorophore | 778 | Metabolic | TNR 9.28 (vs. 4.81 in 5-ALA) |
CH1055 | Fluorophore | 1055 | Passive | TNR: 5.50 ± 0.36 |
Motexafin gadolinium | Fluorophore | 750 | Passive | – |
Cetuximab-IRDye 800CW | Fluorophore | 794 | Molecular | – |
EGF – IRDye 800CW | Fluorophore | 794 | Molecular | – |
Anti-EGFR affibody protein – IRD 800CW | Fluorophore | 794 | Molecular | – |
PEG-Cy5.5 | Fluorophore | 665 | Passive | – |
BLZ-100 | Fluorophore | 700–850 | Molecular | – |
PARPi-FL | Fluorophore | 525 | Molecular | – |
DA364-C5.5 | Fluorophore | 694 | Molecular | – |
GB119-Cy5 | Fluorophore | 665 | Molecular | – |
Angiopep-2-Cy5.5 | Fluorophore | 694 | Molecular | TNR 1.6 |
Chlorotoxin:Cy5.5 | Fluorophore | 694 | Molecular | – |
CLIO-Cy5.5 | Nanoparticle | 694 | Metabolic | – |
QD-RGD | Nanoparticle | 705 | Molecular | TNR 4.42a
|
QD-PEG | Nanoparticle | 705 | Passive | – |
Polyacrylamide NP – F3 | Nanoparticle | Dye dependent | Molecular | n.q.b
|
Lf-MPNA nanogel – Cy5.5 | Nanoparticle | 694 | Molecular | – |
Liposomal EB nanocarrier | Nanoparticle | 680 | Passive | sens 89% spec 100% |
ANG/PEG-UCNPs | Nanoparticle | 800 | Molecular | – |
Lf-SPIO - Cy5.5 | Nanoparticle | 694 | Molecular | TNR 3.8c
|
PLP – Porphyrine | Nanoparticle | 645–730 | Molecular | – |
QD – Anti-EGFR antibody & QD-EGF | Nanoparticle | 635–675 | Molecular | TNR 200–1000 |
GNR – Anti-EGFR antibody | Nanoparticle | 600–1200 | Molecular | – |