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Mass spectrometry imaging for early discovery and development of cancer drugs

1 Division of Developmental Therapeutics, EPOC, National Cancer Center (6-5-1 Kashiwanoha, Kashiwa-shi, Chiba 277-8577, Japan), Japan
2 Synthetic Cellular Chemistry Laboratory, RIKEN (Hirosawa, Wako, Saitama 351-0198, Japan), Japanbr
3 Shimadzu Corporation (1, Nishinokyo-Kuwabaracho, Nakagyo-ku, Kyoto 604-8511, Japan), Japanbr
4 National Cancer Center Hospital (5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan), Japan

Special Issue: Bioinformatics for Cancer Discovery

A drug delivery system (DDS) is a method for delivering a drug to its site of action in the body, with the goal of achieving therapeutic benefits while reducing adverse effects. Pharmacokinetics (PK) and pharmacodynamics (PD) studies have been conducted to evaluate drug delivery, but these approaches are rarely used in the early stages of drug discovery and development. We demonstrated that the tumor stromal barrier inhibits drug distribution within tumor tissue, especially in refractory cancers such as pancreatic cancer. This poses an obstacle to the discovery of new drugs, and is difficult to overcome using conventional in vitro drug discovery methods. In addition, we are also developing new DDS drugs and antibody-drug conjugates (ADCs). These agents act via four steps: Systemic circulation, the enhanced permeability and retention (EPR) effect, penetration within the tumor tissue, and action on cells including controlled drug release. Most of these activities can be evaluated by conventional biological or pharmacological assays. However, it is difficult to examine drug distribution and controlled drug release within targeted tissues. Recent advances in mass spectrometry imaging (MSI) allow examining drug delivery much more conveniently with the off-labeling. A mass microscope, a new type of matrix-associated laser desorption/ionization (MALDI)-MSI analyzer, is a microscope coupled with an atmospheric MALDI and quadruple ion trap time-of-flight (TOF) mass spectrometer, and can provide imaging data with enhanced resolution and high sensitivity. Using a mass microscope, we succeeded in visualizing the EPR effect of a polymeric micelle drug and controlled drug release by an ADC. Currently, we are developing a new drug imaging method using electrospray ionization (ESI)-MSI. Here, we review the use of MSI in early stages of drug discovery and development, as well as our related recent work.
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Keywords drug discovery and development; molecular imaging; mass spectrometry imaging (MSI); drug delivery system (DDS); antibody-drug conjugate (ADC); MALDI (matrix-associated laser desorption/ionization); electrospray ionization (ESI); mass microscope

Citation: Masahiro Yasunaga, Shino Manabe, Masaru Furuta, Koretsugu Ogata, Yoshikatsu Koga, Hiroki Takashima, Toshirou Nishida, Yasuhiro Matsumura. Mass spectrometry imaging for early discovery and development of cancer drugs. AIMS Medical Science, 2018, 5(2): 162-180. doi: 10.3934/medsci.2018.2.162

References

  • 1. Gallo JM (2010) Pharmacokinetic/pharmacodynamic-driven drug development. Mt Sinai J Med N Y 77: 381–388.    
  • 2. Chien JY, Friedrich S, Heathman MA, et al. (2005) Pharmacokinetics/pharmacodynamics and the stages of drug development: Role of modeling and simulation. AAPS J 7: E544–E559.    
  • 3. Garralda E, Dienstmann R, Tabernero J (2017) Pharmacokinetic/pharmacodynamic modeling for drug development in oncology. Am Soc Clin Oncol Educ 37: 210–215.
  • 4. Dingemanse J, Krause A (2017) Impact of pharmacokinetic-pharmacodynamic modelling in early clinical drug development. Eur J Pharm Sci 109S: S53–S58.
  • 5. Glassman PM, Balthasar JP (2014) Mechanistic considerations for the use of monoclonal antibodies for cancer therapy. Cancer Biol Med 11: 20–33.
  • 6. Rajasekaran N, Chester C, Yonezawa A, et al. (2015) Enhancement of antibody-dependent cell mediated cytotoxicity: A new era in cancer treatment. ImmunoTargets Ther 4: 91–100.
  • 7. Krishna M, Nadler SG (2016) Immunogenicity to biotherapeutics-the role of anti-drug immune complexes. Front Immunol 7: 21.
  • 8. Kamath AV (2016) Translational pharmacokinetics and pharmacodynamics of monoclonal antibodies. Drug Discov Today Technol S21–22: 75–83.
  • 9. Gomez-Mantilla JD, Troconiz IF, Parra-Guillen Z, et al. (2014) Review on modeling anti-antibody responses to monoclonal antibodies. J Pharmacokinet Pharmacodyn 41: 523–536.    
  • 10. Adams GP, Weiner LM (2005) Monoclonal antibody therapy of cancer. Nat Biotechnol 23: 1147–1157.    
  • 11. Cornett DS, Reyzer ML, Chaurand P, et al. (2007) Maldi imaging mass spectrometry: Molecular snapshots of biochemical systems. Nat Methods 4: 828–833.    
  • 12. Rompp A, Spengler B (2013) Mass spectrometry imaging with high resolution in mass and space. Histochem Cell Biol 139: 759–783.    
  • 13. Calligaris D, Caragacianu D, Liu X, et al. (2014) Application of desorption electrospray ionization mass spectrometry imaging in breast cancer margin analysis. Proc Natl Acad Sci U. S. A 111: 15184–15189.    
  • 14. Yasunaga M, Manabe S, Tsuji A, et al. (2017) Development of antibody-drug conjugates using dds and molecular imaging. Bioengineering 4: 78.    
  • 15. Wu C, Dill AL, Eberlin LS, et al. (2013) Mass spectrometry imaging under ambient conditions. Mass Spectrom Rev 32: 218–243.    
  • 16. Murray KK, Seneviratne CA, Ghorai S (2016) High resolution laser mass spectrometry bioimaging. Methods 104: 118–126.    
  • 17. Stoeckli M, Chaurand P, Hallahan DE, et al. (2001) Imaging mass spectrometry: A new technology for the analysis of protein expression in mammalian tissues. Nat Med 7: 493–496.    
  • 18. McDonnell LA, Heeren RM (2007) Imaging mass spectrometry. Mass Spectrom Rev 26: 606–643.    
  • 19. Caprioli RM, Farmer TB, Gile J (1997) Molecular imaging of biological samples: Localization of peptides and proteins using maldi-tof ms. Anal Chem 69: 4751–4760.    
  • 20. Wulfkuhle JD, Liotta LA, Petricoin EF (2003) Proteomic applications for the early detection of cancer. Nat Rev Cancer 3: 267–275.    
  • 21. Fujiwara Y, Furuta M, Manabe S, et al. (2016) Imaging mass spectrometry for the precise design of antibody-drug conjugates. Sci Rep 6: 24954.    
  • 22. Yasunaga M, Furuta M, Ogata K, et al. (2013) The significance of microscopic mass spectrometry with high resolution in the visualisation of drug distribution. Sci Rep 3: 3050.
  • 23. Peletier LA, Gabrielsson J (2012) Dynamics of target-mediated drug disposition: Characteristic profiles and parameter identification. J Pharmacokinet Pharmacodyn 39: 429–451.    
  • 24. Pineda C, Jacobs IA, Alvarez DF, et al. (2016) Assessing the immunogenicity of biopharmaceuticals. Biodrugs 30: 195–206.
  • 25. Hampe CS (2012) Protective role of anti-idiotypic antibodies in autoimmunity-lessons for type 1 diabetes. Autoimmunity 45: 320–331.    
  • 26. Thomas A, Teicher BA, Hassan R (2016) Antibody-drug conjugates for cancer therapy. Lancet Oncol 17: e254–e262.    
  • 27. Diamantis N, Banerji U (2016) Antibody-drug conjugates-an emerging class of cancer treatment. Br J Cancer 114: 362–367.    
  • 28. Damelin M, Zhong W, Myers J, et al. (2015) Evolving strategies for target selection for antibody-drug conjugates. Pharm Res 32: 3494–3507.    
  • 29. Senter PD, Sievers EL (2012) The discovery and development of brentuximab vedotin for use in relapsed hodgkin lymphoma and systemic anaplastic large cell lymphoma. Nat Biotechnol 30: 631–637.    
  • 30. Ogitani Y, Aida T, Hagihara K, et al. (2016) Ds-8201a, a novel her2-targeting adc with a novel DNA topoisomerase i inhibitor, demonstrates a promising antitumor efficacy with differentiation from t-dm1. Clin Cancer Res 22: 5097–5108.    
  • 31. Sau S, Alsaab HO, Kashaw SK, et al. (2017) Advances in antibody-drug conjugates: A new era of targeted cancer therapy. Drug Discovery Today 22: 1547–1556.    
  • 32. Mitsunaga M, Ogawa M, Kosaka N, et al. (2011) Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Nat Med 17: 1685–1691.    
  • 33. Larson SM, Carrasquillo JA, Cheung NK, et al. (2015) Radioimmunotherapy of human tumours. Nat Rev Cancer 15: 347–360.    
  • 34. Sau S, Alsaab HO, Kashaw SK, et al. (2017) Advances in antibody-drug conjugates: A new era of targeted cancer therapy. Drug Discovery Today.
  • 35. Gerber HP, Sapra P, Loganzo F, et al. (2016) Combining antibody-drug conjugates and immune-mediated cancer therapy: What to expect? Biochem Pharmacol 102: 1–6.    
  • 36. Alsaab HO, Sau S, Alzhrani R, et al. (2017) Pd-1 and pd-l1 checkpoint signaling inhibition for cancer immunotherapy: Mechanism, combinations, and clinical outcome. Front Pharmacol 8: 561.    
  • 37. Matsumura Y (2014) The drug discovery by nanomedicine and its clinical experience. Jpn J Clin Oncol 44: 515–525.    
  • 38. Nishiyama N, Matsumura Y, Kataoka K (2016) Development of polymeric micelles for targeting intractable cancers. Cancer Sci 107: 867–874.    
  • 39. Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46: 6387–6392.
  • 40. Cabral H, Matsumoto Y, Mizuno K, et al. (2011) Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol 6: 815–823.    
  • 41. Oku N (2017) Innovations in liposomal dds technology and its application for the treatment of various diseases. Biol Pharm Bull 40: 119–127.    
  • 42. Kinoshita R, Ishima Y, Chuang VTG, et al. (2017) Improved anticancer effects of albumin-bound paclitaxel nanoparticle via augmentation of epr effect and albumin-protein interactions using s-nitrosated human serum albumin dimer. Biomaterials 140: 162–169.    
  • 43. Duncan R (2006) Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer 6: 688–701.    
  • 44. Yokoyama M (2014) Polymeric micelles as drug carriers: Their lights and shadows. J Drug Targeting 22: 576–583.    
  • 45. Jain RK, Stylianopoulos T (2010) Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol 7: 653–664.    
  • 46. Allen TM, Cullis PR (2013) Liposomal drug delivery systems: From concept to clinical applications. Adv Drug Delivery Rev 65: 36–48.    
  • 47. Bae Y, Nishiyama N, Fukushima S, et al. (2005) Preparation and biological characterization of polymeric micelle drug carriers with intracellular ph-triggered drug release property: Tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy. Bioconjugate Chem 16: 122–130.    
  • 48. Kraft JC, Freeling JP, Wang Z, et al. (2014) Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems. J Pharm Sci 103: 29–52.    
  • 49. Rao W, Pan N, Yang Z (2016) Applications of the single-probe: Mass spectrometry imaging and single cell analysis under ambient conditions. J Visualized Exp JoVE 2016: 53911.
  • 50. Calligaris D, Feldman DR, Norton I, et al. (2015) Molecular typing of meningiomas by desorption electrospray ionization mass spectrometry imaging for surgical decision-making. Int J Mass Spectrom 377: 690–698.    
  • 51. Fenn JB, Mann M, Meng CK, et al. (1989) Electrospray ionization for mass spectrometry of large biomolecules. Science 246: 64–71.    
  • 52. Takats Z, Wiseman JM, Gologan B, et al. (2004) Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306: 471–473.    
  • 53. Parrot D, Papazian S, Foil D, et al. (2018) Imaging the unimaginable: Desorption electrospray ionization-imaging mass spectrometry (desi-ims) in natural product research. Planta Med.
  • 54. Cooks RG, Ouyang Z, Takats Z, et al. (2006) Detection technologies. Ambient mass spectrometry. Science 311: 1566–1570.
  • 55. Zimmerman TA, Monroe EB, Tucker KR, et al. (2008) Chapter 13: Imaging of cells and tissues with mass spectrometry: Adding chemical information to imaging. Methods Cell Biol 89: 361–390.    
  • 56. Signor L, Boeri EE (2013) Matrix-assisted laser desorption/ionization time of flight (maldi-tof) mass spectrometric analysis of intact proteins larger than 100 kda. J Visualized Exp JoVE 108: e50635.
  • 57. Sudhir PR, Wu HF, Zhou ZC (2005) Identification of peptides using gold nanoparticle-assisted single-drop microextraction coupled with ap-maldi mass spectrometry. Anal Chem 77: 7380–7385.    
  • 58. Abdelhamid HN, Wu HF (2012) A method to detect metal-drug complexes and their interactions with pathogenic bacteria via graphene nanosheet assist laser desorption/ionization mass spectrometry and biosensors. Anal Chim Acta 751: 94–104.    
  • 59. Abdelhamid HN, Wu HF (2013) Furoic and mefenamic acids as new matrices for matrix assisted laser desorption/ionization-(maldi)-mass spectrometry. Talanta 115: 442–450.    
  • 60. Nasser AH, Wu BS, Wu HF (2014) Graphene coated silica applied for high ionization matrix assisted laser desorption/ionization mass spectrometry: A novel approach for environmental and biomolecule analysis. Talanta 126: 27–37.    
  • 61. Abdelhamid HN, Wu HF (2015) Synthesis of a highly dispersive sinapinic acid@graphene oxide (sa@go) and its applications as a novel surface assisted laser desorption/ionization mass spectrometry for proteomics and pathogenic bacteria biosensing. Analyst 140: 1555–1565.    
  • 62. Abdelhamid HN, Wu HF (2016) Gold nanoparticles assisted laser desorption/ionization mass spectrometry and applications: From simple molecules to intact cells. Anal Bioanal Chem 408: 4485–4502.    
  • 63. Harada T, Yuba-Kubo A, Sugiura Y, et al. (2009) Visualization of volatile substances in different organelles with an atmospheric-pressure mass microscope. Anal Chem 81: 9153–9157.    
  • 64. Saito Y, Waki M, Hameed S, et al. (2012) Development of imaging mass spectrometry. Biol Pharm Bull 35: 1417–1424.    
  • 65. Sugiura Y, Honda K, Suematsu M (2015) Development of an imaging mass spectrometry technique for visualizing localized cellular signaling mediators in tissues. Mass Spectrom 4: A0040.    
  • 66. Setou M, Kurabe N (2011) Mass microscopy: High-resolution imaging mass spectrometry. J Electron Microsc 60: 47–56.    
  • 67. Maeda H (2001) Smancs and polymer-conjugated macromolecular drugs: Advantages in cancer chemotherapy. Adv Drug Delivery Rev 46: 169–185.    
  • 68. Barenholz Y (2012) Doxil(r)-the first fda-approved nano-drug: Lessons learned. J Controlled Release 160: 117–134.    
  • 69. Giordano G, Pancione M, Olivieri N, et al. (2017) Nano albumin bound-paclitaxel in pancreatic cancer: Current evidences and future directions. World J Gastroenterol 23: 5875–5886.    
  • 70. Kogure K, Akita H, Yamada Y, et al. (2008) Multifunctional envelope-type nano device (mend) as a non-viral gene delivery system. Adv Drug Delivery Rev 60: 559–571.    
  • 71. Sugaya A, Hyodo I, Koga Y, et al. (2016) Utility of epirubicin-incorporating micelles tagged with anti-tissue factor antibody clone with no anticoagulant effect. Cancer Sci 107: 335–340.    
  • 72. Hiyama E, Ali A, Amer S, et al. (2015) Direct lipido-metabolomics of single floating cells for analysis of circulating tumor cells by live single-cell mass spectrometry. Anal Sci 31: 1215–1217.    
  • 73. Hamaguchi T, Matsumura Y, Suzuki M, et al. (2005) Nk105, a paclitaxel-incorporating micellar nanoparticle formulation, can extend in vivo antitumour activity and reduce the neurotoxicity of paclitaxel. Br J Cancer 92: 1240–1246.    
  • 74. Verma S, Miles D, Gianni L, et al. (2012) Trastuzumab emtansine for her2-positive advanced breast cancer. N Engl J Med 367: 1783–1791.    
  • 75. Younes A, Gopal AK, Smith SE, et al. (2012) Results of a pivotal phase ii study of brentuximab vedotin for patients with relapsed or refractory hodgkin's lymphoma. J Clin Oncol 30: 2183–2189.    
  • 76. Pro B, Advani R, Brice P, et al. (2012) Brentuximab vedotin (sgn-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: Results of a phase ii study. J Clin Oncol 30: 2190–2196.    
  • 77. Doronina SO, Toki BE, Torgov MY, et al. (2003) Development of potent monoclonal antibody auristatin conjugates for cancer therapy. Nat Biotechnol 21: 778–784.    
  • 78. Lyon RP, Bovee TD, Doronina SO, et al. (2015) Reducing hydrophobicity of homogeneous antibody-drug conjugates improves pharmacokinetics and therapeutic index. Nat Biotechnol 33: 733–735.    
  • 79. Hisada Y, Yasunaga M, Hanaoka S, et al. (2013) Discovery of an uncovered region in fibrin clots and its clinical significance. Sci Rep 3: 2604.    
  • 80. Takashima H, Tsuji AB, Saga T, et al. (2017) Molecular imaging using an anti-human tissue factor monoclonal antibody in an orthotopic glioma xenograft model. Sci Rep 7: 12341.    
  • 81. Koga Y, Manabe S, Aihara Y, et al. (2015) Antitumor effect of antitissue factor antibody-mmae conjugate in human pancreatic tumor xenografts. Int J Cancer 137: 1457–1466.    
  • 82. Rao W, Celiz AD, Scurr DJ, et al. (2013) Ambient desi and lesa-ms analysis of proteins adsorbed to a biomaterial surface using in-situ surface tryptic digestion. J Am Soc Mass Spectrom 24: 1927–1936.    
  • 83. Takahashi T, Serada S, Ako M, et al. (2013) New findings of kinase switching in gastrointestinal stromal tumor under imatinib using phosphoproteomic analysis. Int J Cancer 133: 2737–2743.
  • 84. Emara S, Amer S, Ali A, et al. (2017) Single-cell metabolomics. Adv Exp Med Biol 965: 323–343.    
  • 85. Matsumura Y (2012) Cancer stromal targeting (cast) therapy. Adv Drug Delivery Rev 64: 710–719.    
  • 86. Yasunaga M, Manabe S, Tarin D, et al. (2011) Cancer-stroma targeting therapy by cytotoxic immunoconjugate bound to the collagen 4 network in the tumor tissue. Bioconjugate Chem 22: 1776–1783.    
  • 87. Yasunaga M, Manabe S, Tarin D, et al. (2013) Tailored immunoconjugate therapy depending on a quantity of tumor stroma. Cancer Sci 104: 231–237.    
  • 88. Yasunaga M, Manabe S, Matsumura Y (2017) Immunoregulation by il-7r-targeting antibody-drug conjugates: Overcoming steroid-resistance in cancer and autoimmune disease. Sci Rep 7: 10735.    

 

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