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Optimizing singlet oxygen dosimetry for photodynamic therapy (PDT)

Award Number: R01EB032821
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Optimizing singlet oxygen dosimetry for photodynamic therapy (PDT) - Optimizing Singlet Oxygen Dosimetry for Photodynamic Therapy (PDT) Abstract The overall objective of this project is to optimize clinical singlet oxygen (1O2) dosimetry (SOD) via three complementary and competing technologies: time-resolved singlet oxygen luminescence dosimetry (TSOLD), multispectral singlet oxygen luminescence dosimetry (MSOLD), and singlet oxygen explicit dosimetry (SOED). The TSOLD instrument is optical fiber-based and achieves ultralow noise detection via infrared time-correlated single-photon counting. It can be used before and after PDT to measure cytotoxic 1O2 concentration ([1O2]) generation in tumor based on its 1270 nm luminescence emission, since it utilizes a short (ns) pulsed laser for 1O2 excitation that is independent of the PDT treatment laser. The recently developed MSOLD instrument measures the luminescence spectrum of singlet oxygen excited by the treatment light, it is thus capable of monitoring [1O2] during PDT without interfering with the treatment. However, unlike TSOLD, MSOLD may introduce additional uncertainty in [1O2] due to a phosphorescence background orders of magnitude larger than the singlet oxygen signal. The SOED instrument can be used in-vivo during PDT in real-time to measure reacted 1O2 generated by the treatment light based on explicit measurement of the light fluence rate, tissue oxygen concentration, and photosensitizer concentration. The TSOLD or MSOLD signals will be used as an input to the SOED system to make it more robust to account for the local oxygen microenvironment. Here, the immediate clinical translation is to compare and determine the most suitable combination of the three technologies for SOD by measurements at multiple sites in patients undergoing intrapleural PDT for malignant pleural mesothelioma, which has shown significant potential in Photofrin-mediated clinical trials at UPenn. In addition, comparison will be made in photosensitizer solutions, tissue-simulating phantoms, and tumors in vivo under well-controlled conditions across a wide range of treatment conditions. Correlation of the tumor response with the1O2 measurements will be evaluated for three clinical photosensitizers (Photofrin, BPD, and ALA) in preclinical models. The SOED instrument will be used at the same time and locations to calculate the “explicit” light-drug- oxygen dose parameters as well as the tissue optical properties. The latter will be used to correct the measured 1O2 signal for light attenuation in order to calculate, the absolute concentration of the cytotoxic agent. The explicit dose parameters will be used as inputs for SOED in an established macroscopic biophysical model to predict the instantaneous and cumulative singlet oxygen concentration ([1O2]) for comparison with TSOLD and MSOLD results, respectively. The outcome of this project will be the determination of the optimal combination (TSOLD/MSOLD/SOED) for SOD in an ongoing PDT mesothelioma clinical trial under clinically-relevant conditions. We hypothesize that quantitative SOD will be significantly more predictive of PDT efficacy than the explicit or implicit (photobleaching-based) techniques used at present. Moreover, we hypothesize that the optimized SOD system will give real-time feedback so that treatment can be personalized.


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: 2025 ( Subtotal = $480,118 )
2025	2025	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	3/25/2025	NON-COMPETING CONTINUATION	$480,118
														Subtotal = $480,118

Issue Date FY: 2024 ( Subtotal = $733,087 )
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	3/13/2024	NON-COMPETING CONTINUATION	$498,421
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	3	9/5/2024	SUPPLEMENT FOR EXPANSION	$190,361
2024	2024	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	6/7/2024	NON-COMPETING CONTINUATION	$44,305
														Subtotal = $733,087

Issue Date FY: 2023 ( Subtotal = $558,683 )
2023	2023	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	3/14/2023	NON-COMPETING CONTINUATION	$558,683
2023	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	1/26/2023	NEW	$0
														Subtotal = $558,683

Issue Date FY: 2022 ( Subtotal = $550,210 )
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	6/22/2022	NEW	$550,210
														Subtotal = $550,210

Grand Total All Awards = $2,322,098

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Optimizing singlet oxygen dosimetry for photodynamic therapy (PDT)

Award Number: R01EB032821

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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