Development of adcs using molecular imaging

Masahiro Yasunaga, Shino Manabe, Atsushi Tsuji, Mamoru Furuta, Koretsugu Ogata, Yoshikatsu Koga, Yuki Fujiwara, Tsuneo Saga, Yasuhiro Matsumura

Research output: Contribution to journalReview article

Abstract

Antibody-drug conjugates (ADCs) comprise an antibody, a linker, and a drug or payload. The selection of a tumor-specific antibody and development of a linker having an efficient controlled drug release (CDR) are critical steps in developing a fully functional and eŠective ADC. In our research strategy, molecular imaging technologies have been employed to evaluate the efficiency of antibody delivery and CDR of the linker. In preclinical setting, antibody delivery into the tumor area or antibody penetration through the tumor stroma in malignant lymphoma or pancreatic tumor was evaluated by in vivo fluorescence imaging technique. Positron emission tomography (PET) imaging studies were conducted using89 Zr-labeled antibody to evaluate tumor targeting in a spontaneous carcinogenesis model. The model had dense stroma and was pathophysiologically very similar to human cancer. The drug imaging system, using microscopic mass spectroscopy (MMS) with enhanced resolution and sensitivity, was used for the evaluation of CDR. Paclitaxel (PTX)-incorporated micelle, a high-molecular-weight (HMW) carrier with CDR, showing similar properties as those of ADC, was analyzed. In contrast to free PTX, micelle selectively increased drug accumulation into the tumor and reduced toxicity in normal tissues by the enhanced permeability and retention (EPR) eŠect. Our drug imaging system has been used recently to evaluate the CDR of the ADC-linker. We present our work on the development of ADC using a molecular imaging technique.

Original languageEnglish
Pages (from-to)535-544
Number of pages10
JournalYakugaku Zasshi
Volume137
Issue number5
DOIs
Publication statusPublished - 2017 Jan 1
Externally publishedYes

Keywords

  • Antibody
  • Antibody-drug conjugate
  • Drug delivery system
  • Molecular imaging
  • MS imaging

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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  • Cite this

    Yasunaga, M., Manabe, S., Tsuji, A., Furuta, M., Ogata, K., Koga, Y., Fujiwara, Y., Saga, T., & Matsumura, Y. (2017). Development of adcs using molecular imaging. Yakugaku Zasshi, 137(5), 535-544. https://doi.org/10.1248/yakushi.16-00255-3