Mass spectrometry imaging for early discovery and development of cancer drugs

Masahiro Yasunaga; Shino Manabe; Masaru Furuta; Koretsugu Ogata; Yoshikatsu Koga; Hiroki Takashima; Toshirou Nishida; Yasuhiro Matsumura; Masahiro Yasunaga; Shino Manabe; Masaru Furuta; Koretsugu Ogata; Yoshikatsu Koga; Hiroki Takashima; Toshirou Nishida; Yasuhiro Matsumura

doi:10.3934/medsci.2018.2.162

AIMS Medical Science

2018, Volume 5, Issue 2: 162-180. doi: 10.3934/medsci.2018.2.162

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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

Received: 20 December 2017 Accepted: 28 March 2018 Published: 15 April 2018

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.
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[J]. AIMS Medical Science, 2018, 5(2): 162-180. doi: 10.3934/medsci.2018.2.162

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Abstract

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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