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Quantitative Fluorescence Imaging-Guided Detection and Targeted Therapy Monitoring Platform for Ovarian Cancer Micrometastases

Award Number: R01CA243164
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $14,873 )
2024	2022	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Detection and Diagnosis Research	002	4	1/18/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$14,873
2024	2022	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	4	11/7/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$211,498
2024	2021	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Cancer Detection and Diagnosis Research	000	2	11/7/2023	NON-COMPETING CONTINUATION	-$211,498
														Subtotal = $14,873

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	4	3/29/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$329,592
2023	2022	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Cancer Detection and Diagnosis Research	000	3	3/29/2023	NON-COMPETING CONTINUATION	-$329,592
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $329,592 )
2022	2022	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Cancer Detection and Diagnosis Research	000	3	4/21/2022	NON-COMPETING CONTINUATION	$329,592
														Subtotal = $329,592

Issue Date FY: 2021 ( Subtotal = $336,645 )
2021	2021	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Cancer Detection and Diagnosis Research	000	2	4/23/2021	NON-COMPETING CONTINUATION	$336,645
														Subtotal = $336,645

Issue Date FY: 2020 ( Subtotal = $340,883 )
2020	2020	WRIGHT STATE UNIVERSITY	3640 COLONEL GLENN HWY	DAYTON	OH	45435	GREENE	USA	Cancer Detection and Diagnosis Research	000	1	7/17/2020	NEW	$340,883
														Subtotal = $340,883

Grand Total All Awards = $1,021,993

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Quantitative Fluorescence Imaging-Guided Detection and Targeted Therapy Monitoring Platform for Ovarian Cancer Micrometastases

Award Number: R01CA243164

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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