Mass spectrometry imaging for early discovery and development of cancer drugs

AIMS Medical Science

article

Masahiro Yasunaga¹  Shino Manabe²  Masaru Furuta³  Koretsugu Ogata³  Yoshikatsu Koga⁴  Hiroki Takashima⁴  Toshirou Nishida⁵  Yasuhiro Matsumura¹ 

[1] Division of Developmental Therapeutics, EPOC, National Cancer Center;Synthetic Cellular Chemistry Laboratory, RIKEN;Shimadzu Corporation;Division of Developmental Therapeutics, National Cancer Center;National Cancer Center Hospital

关键词: 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;    ;   

DOI  :  10.3934/medsci.2018.2.162

来源: American Institute of Mathematical Sciences

【 摘 要 】

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.

【 授权许可】

CC BY