Open AccessSemiquantitative assessment of the microdistribution of fluorescence‐labeled monoclonal antibody in small peritoneal disseminations of ovarian cancer
Author(s) -
Kosaka Nobuyuki,
Ogawa Mikako,
Paik David S.,
Paik Chang H.,
Choyke Peter L.,
Kobayashi Hisataka
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01423.x
Subject(s) - trastuzumab , monoclonal antibody , antibody , medicine , cancer , chemistry , pathology , microbiology and biotechnology , immunology , biology , breast cancer
( Cancer Sci 2010; 101: 820–825) Uniform antibody microdistribution throughout tumor nodules is crucial for antibody‐targeted therapy, because non‐uniform microdistribution leads to suboptimal therapeutic effect, a commonly observed limitation of therapeutic antibodies. Herein, we evaluated the microdistribution of different doses of intraperitoneally injected fluorescence‐labeled full‐antibody trastuzumab (15, 50, and 150 μg) and its Fab fragment (trastuzumab‐Fab: 15 and 50 μg) in a mouse model of ovarian cancer with peritoneal disseminated tumor. A semiquantitative approach (central/peripheral accumulation ratio; C/P ratio) was developed using in situ fluorescence microscopy. Furthermore, we compared the microdistribution of intact trastuzumab with a mixed injection of trastuzumab and trastuzumab‐Fab or serial injections of trastuzumab using in situ multicolor fluorescence microscopy. Fluorescence images after the administration of 15 or 50 μg trastuzumab and 15 μg trastuzumab‐Fab demonstrated antibody accumulation in the tumor periphery, whereas administration of 150 μg trastuzumab and 50 μg trastuzumab‐Fab showed relatively uniform accumulation throughout the tumor nodule. Using serial injections (19‐h interval) of trastuzumab‐rhodamine green and carboxytetramethylrhodamine (TAMRA), it was observed that the latterly injected trastuzumab‐TAMRA was distributed more centrally than trastuzumab‐rhodamine green injected first, whereas no difference was observed in the control mixed‐injection group. Moreover, the mixed injection of trastuzumab and trastuzumab‐Fab showed that trastuzumab‐Fab distributed more centrally than the same amount of co‐injected trastuzumab. Our results suggest that the strategies of increasing dose and using Fab fragments can be used to achieve a uniform antibody distribution within peritoneal disseminated nodules after intraperitoneal injection. Furthermore, serial‐injection and mixed‐injection strategies can modify antibody microdistribution within tumors and have the potential for preferential delivery of anticancer drugs to either the tumor periphery or its center.