Early imaging of tumor response to chemotherapy has the potential for significant clinical benefits. We are developing a
family of fiber-optic sensors called SencilsTM (sensory cilia), which are disposable, minimally invasive, and can provide
in vivo monitoring of various analytes for several weeks. The objective of this study was to develop and test our sensor to
image the labeling of phosphatidylserine by apoptotic cells in response to chemotherapeutic drugs. FM1-43 was a better
fluorescent marker for detecting phosphatidylserine expression than Annexin V-FITC; both the proportion of labeled
cells (Annexin V, 15%; FM1-43, 58%) and the relative fluorescent increase (Annexin V-FITC, 1.5-fold; FM1-43,
4.5-fold) was greater when FM1-43 was used to detect apoptosis. Initial testing of the optical sensing technology using
Taxol-treated MCF-7 cells demonstrated that injection of FM1-43 resulted in a rapid, transient increase in fluorescence
that was greater in apoptotic cells compared to control cells (apoptotic cells, 4-fold increase; control cells, 2-fold
increase). Using an established animal model, mice were injected with cyclophosphamide and hepatic apoptosis was
assessed by imaging of PS expression. Both the amplitude of fluorescence increase and the time taken for the amplitude
to decay to half of its peak were increased in livers from animals treated with cyclophosphamide. Our optical sensing
technology can be used to detect the early apoptotic response of cells to chemotherapeutic drugs both in vitro and in vivo.
This novel technology represents a unique option for the imaging of tumor responses in vivo, and provides an inexpensive, specific system for the detection of early-stage apoptosis.