The microdistribution of therapeutic monoclonal antibodies within a tumor is important for determining clinical response.
Nonuniform microdistribution predicts therapy failure. Herein, we developed a semiquantitative method for measuring
microdistribution of an antibody within a tumor using in situ fluorescence microscopy and sought to modulate the
microdistribution by altering the route and timing of antibody dosing. The microdistribution of a fluorescently-labeled
antibody, trastuzumab (50-μg and 150-μg intraperitoneal injection (i.p.), and 100-μg intravenous injection (i.v.)) was
evaluated in a peritoneal dissemination mouse model of ovarian cancer. In addition, we evaluated the microdistribution
of concurrently-injected (30-μg i.p. and 100-μg i.v.) or serial (two doses of 30-μg i.p.) trastuzumab using in situ
multicolor fluorescence microscopy. After the administration of 50-μg i.p. and 100-μg i.v. trastuzumab fluorescence
imaging showed no significant difference in the central to peripheral signal ratio (C/P ratio) and demonstrated a
peripheral-dominant accumulation, whereas administration of 150-μg i.p. trastuzumab showed relatively uniform, central
dominant accumulation. With concurrent-i.p.-i.v. injections trastuzumab showed slightly higher C/P ratio than
concurrently-injected i.p. trastuzumab. Moreover, in the serial injection study, the second injection of trastuzumab
distributed more centrally than the first injection, while no difference was observed in the control group. Our results
suggest that injection routes do not affect the microdistribution pattern of antibody in small peritoneal disseminations.
However, increasing the dose results in a more uniform antibody distribution within peritoneal nodules. Furthermore, the
serial i.p. injection of antibody can modify the microdistribution within tumor nodules. This work has implications for
the optimal delivery of antibody based cancer therapies.