PROJECT SUMMARY/ABSTRACT
A major challenge in the management of advanced ovarian cancer is the presence of disseminated
microscopic tumor nodules within the intraperitoneal cavity. Despite surgery and adjuvant chemotherapy, as
many as 50% of patients can show occult disseminated disease, with only a 43% survival rate. Furthermore,
systemic chemotherapy can have toxic side effects. Thus, recent efforts have aimed at improving detection
and treatment of micromets. Chemophototherapy (CPT), the combination of chemotherapy and photodynamic
therapy, is an emerging cancer treatment modality that can provide synergistic efficacy of both therapies. The
overall goal is to implement a quantitative laparoscopic imaging and treatment approach for advanced
detection of micromets and optimization of CPT for targeted destruction of ovarian micromets and reduced
toxic side effects. Quantitative fluorescence laparoscopic imaging will provide high sensitivity and resolution for
detecting micromets as well as image guided drug delivery. Folate receptor alpha (FA) will be used as a
promising target because it is highly specific of epithelial ovarian cancer. The proposed targeted CPT
compound has a ~6-fold tumor-specificity providing enhanced fluorescence contrast. These folate-targeted,
porphyrin-phospholipid doped liposomes are triggered directly by near infrared (NIR) light. This activates the
anti-cancer photosensitizer outer layer and releases the anti-cancer agent Doxorubicin (Dox). While this
nanocarrier is expected to improve detection of micromets, tissue absorption and scattering in living tissue can
confound fluorescence contrast. Quantitative imaging based on spatial frequency domain imaging can
eliminate these confounding effects and provide quantitative contrasts to enable more sensitive detection
compared to raw fluorescence or white light visualization. Furthermore, this quantitative capability can function
in near-real-time to provide feedback on drug release, thus allowing image-guided optimization of treatment
light to ensure full drug release within each tumor. In Aim 1, a wide-field dual-channel laparoscope, fast
quantification algorithms and targeted liposomal nano-construct will be implemented and optimized. In Aim 2,
the platform will be validated in vivo for improved detection of micromets vs. raw fluorescence and white light.
In Aim 3, the platform’s efficacy will be validated in vivo for destroying micromets in targeted tumors while
reducing toxicity to surrounding normal tissues. Successful completion of this approach is expected to result in
improved detection and treatment of micromets with reduced side effects. This is ultimately expected to lead to
reduced recurrence rates and overall improved survival. Although this imaging approach focuses on epithelial
ovarian cancer diagnosis and treatment, it can be applicable to a wide range of epithelial diseases, such as
oral, lung, and gastrointestinal cancers.