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Development of Antibody–Drug Conjugates Using DDS and Molecular Imaging

1
Division of Developmental Therapeutics, EPOC, National Cancer Center, Kashiwa 277-8577, Japan
2
Synthetic Cellular Chemistry Laboratory, RIKEN, Wako 351-0198, Japan
3
Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, QST, Chiba 263-8555, Japan; abtsuji+[email protected]
4
Shimadzu Corporation, Kyoto 604-8511, Japan
5
Department of Diagnostic Radiology, Kyoto University Hospital; Kyoto 606-8501, Japan
*
Author to whom correspondence should be addressed.
Academic Editors: Ramana Pidaparti and Hu Yang
Bioengineering 2017, 4(3), 78; https://doi.org/10.3390/bioengineering4030078
Received: 30 August 2017 / Revised: 13 September 2017 / Accepted: 14 September 2017 / Published: 17 September 2017
(This article belongs to the Special Issue Advanced Drug Delivery Systems and Devices)
Antibody-drug conjugate (ADC), as a next generation of antibody therapeutics, is a combination of an antibody and a drug connected via a specialized linker. ADC has four action steps: systemic circulation, the enhanced permeability and retention (EPR) effect, penetration within the tumor tissue, and action on cells, such as through drug delivery system (DDS) drugs. An antibody with a size of about 10 nm has the same capacity for passive targeting as some DDS carriers, depending on the EPR effect. In addition, some antibodies are capable of active targeting. A linker is stable in the bloodstream but should release drugs efficiently in the tumor cells or their microenvironment. Thus, the linker technology is actually a typical controlled release technology in DDS. Here, we focused on molecular imaging. Fluorescent and positron emission tomography (PET) imaging is useful for the visualization and evaluation of antibody delivery in terms of passive and active targeting in the systemic circulation and in tumors. To evaluate the controlled release of the ADC in the targeted area, a mass spectrometry imaging (MSI) with a mass microscope, to visualize the drug released from ADC, was used. As a result, we succeeded in confirming the significant anti-tumor activity of anti-fibrin, or anti-tissue factor-ADC, in preclinical settings by using DDS and molecular imaging. View Full-Text
Keywords: ADC (antibody-drug conjugate); DDS (drug delivery system); molecular imaging; antibody delivery; controlled release; PET (positron emission tomography); MSI (mass spectrometry imaging) ADC (antibody-drug conjugate); DDS (drug delivery system); molecular imaging; antibody delivery; controlled release; PET (positron emission tomography); MSI (mass spectrometry imaging)
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Yasunaga, M.; Manabe, S.; Tsuji, A.; Furuta, M.; Ogata, K.; Koga, Y.; Saga, T.; Matsumura, Y. Development of Antibody–Drug Conjugates Using DDS and Molecular Imaging. Bioengineering 2017, 4, 78.

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