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Principal Investigator: Ulas Sunar
Organization: STATE UNIVERSITY NEW YORK STONY BROOK
Fiscal Year: 2024
Award: $1
Funding agency: National Cancer Institute
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.
Terms: <14-Hydroxydaunomycin><Abscission><Acids><Actinotherapy><Address><Adjuvant Chemotherapy><Adjuvant Drug Therapy><Adriamycine><Adult Folate Receptor 1><Adult Folate-Binding Protein><Algorithms><Anti-Cancer Agents><Antineoplastic Agents><Antineoplastic Drugs><Antineoplastics><Biodistribution><Biopsy><Body Tissues><Cancer Drug><Cancer Patient><Cancer Treatment><Cancers><Celioscopes><Cell Communication and Signaling><Cell Culture Techniques><Cell Line><Cell Signaling><CellLine><Clinic><Clinical><Combination Drug Therapy><Data><Detection><Diagnosis><Disease><Disorder><Dose><Doxorubicin><Doxorubicina><Drug Targeting><Drugs><Ensure><Epithelial ovarian cancer><Epithelium><Excision><Exposure to><Extirpation><FOLR><FOLR1><FOLR1 gene><Feedback><Fluorescence><Folate><Folate Receptor Alpha><Folic Acid><GI cancers><GI malignancies><GI tract cancers><Gastrointestinal Cancer><Gastrointestinal Tract Cancer><Goals><Hydroxyl Daunorubicin><Hydroxyldaunorubicin><Illumination><Image><Imaging technology><In Vitro><Intracellular Communication and Signaling><Kinetics><Laparoscopes><Lead><Lesion><Light><Light Therapy><Lighting><Lipids><Liposomal><Liposomes><MICMET><MOv18><Malignant Cell><Malignant Gastrointestinal Neoplasm><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Oral Cavity Neoplasm><Malignant Oral Cavity Tumor><Malignant Oral Neoplasm><Malignant Ovarian Neoplasm><Malignant Ovarian Tumor><Malignant Tumor><Malignant Tumor of the Lung><Malignant Tumor of the Ovary><Malignant neoplasm of gastrointestinal tract><Malignant neoplasm of lung><Malignant neoplasm of ovary><Maps><Medication><Metastasis><Metastasis to Ovary><Metastasize><Metastatic Lesion><Metastatic Malignant Neoplasm to the Ovary><Metastatic Malignant Tumor to the Ovary><Metastatic Mass><Metastatic Neoplasm><Metastatic Tumor><Micrometastasis><Micromets><Microscopic><Modality><Monitor><Mouth Cancer><Neoplasm Metastasis><Neoplastic Disease Chemotherapeutic Agents><Nodule><Normal Tissue><Normal tissue morphology><Operative Procedures><Operative Surgical Procedures><Oral Cancer><Ovarian><Ovarian Cancer-Associated Antigen><Ovarian Carcinoma><Ovarian Metastasis><Ovary Cancer><Ovary Carcinoma><PUVA><PUVA Photochemotherapy><Patients><Pb element><Peritoneoscopes><Pharmaceutical Preparations><Phosphatides><Phospholipids><Photochemotherapy><Photodynamic Therapy><Photoradiation><Photoradiation Therapy><Photosensitizers><Photosensitizing Agents><Phototherapy><Physiologic><Physiological><Platinum><Platinum Black><Polychemotherapy><Porphyrins><Protocol><Protocols documentation><Pt element><Pteroylglutamic Acid><Public Health><Pulmonary Cancer><Pulmonary malignant Neoplasm><QOL><Quality of life><Recurrence><Recurrent><Removal><Resistance><Resolution><Scheme><Secondary Neoplasm><Secondary Tumor><Sensitivity and Specificity><Shapes><Signal Transduction><Signal Transduction Systems><Signaling><Spatial Frequency Domain Imaging><Specificity><Strains Cell Lines><Structure><Surface><Surgical><Surgical Interventions><Surgical Procedure><Surgical Removal><Survival Rate><System><Technology><Therapeutic><Time><Tissues><Toxic effect><Toxicities><Translating><Treatment Efficacy><Treatment-related toxicity><Tumor-Specific Treatment Agents><Visualization><Vitamin M><absorption><anti-cancer><anti-cancer drug><anti-cancer therapy><attenuation><biological signal transduction><cancer cell><cancer diagnosis><cancer metastasis><cancer therapy><cancer-directed therapy><cell culture><cell cultures><chemotherapy><combination chemotherapy><combination pharmacotherapy><contrast enhanced><controlled release><cultured cell line><deep learning><deep learning algorithm><deep learning method><deep learning strategy><drug/agent><fluorescence imaging><fluorescent imaging><gastrointestinal malignancies><heavy metal Pb><heavy metal lead><image guidance><image guided><image guided therapy><image-based method><image-guided drug delivery><imaging><imaging approach><imaging based approach><imaging detection><imaging method><imaging modality><imaging platform><imaging-based detection><imaging-based disease detection><improved><in vivo><intervention efficacy><intraperitoneal><light intervention><light treatment><liposomal carrier><liposomal nanocarrier><liposomal vehicle><liposome vector><lung cancer><malignancy><malignant mouth neoplasm><malignant mouth tumor><nano><nano medicinal><nano medicine><nanocarrier><nanomedicinal><nanomedicine><nanovessel><neoplasm/cancer><neoplasm/cancer photoradiation therapy><novel><optic imaging><optical imaging><oral cavity cancer><ovarian cancer><phantom model><photosensitizer><quantitative imaging><resection><resistant><resolutions><side effect><spatiotemporal><surgery><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapeutic efficacy><therapeutic toxicity><therapy associated toxicity><therapy efficacy><therapy optimization><therapy related toxicity><therapy toxicity><treatment optimization><treatment toxicity><treatment-associated toxicity><tumor><tumor cell metastasis><tumor specificity><uptake><vitamin Bc>