Wednesday, July 16, 2025 7/16/2025

Imaging and Dosimetry of Yttrium-90 for Personalized Cancer Treatment

Award Number: R01EB022075
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: 09/15/2016
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Imaging and Dosimetry of Yttrium-90 for Personalized Cancer Treatment - Abstract Selective internal radiation therapy (SIRT) with preferential delivery of 90Y microspheres to target lesions has shown promising response rates with limited toxicity in the treatment of hepatocellular (HCC), the second leading cause of cancer death in the world. However, to achieve more durable responses, there is much room to improve/adapt the treatment to ensure that all lesions and lesion sub-regions receive adequate radiation delivery. While externally delivered stereotactic body radiation therapy (SBRT) is well suited for smaller solitary HCC, its application for larger or multifocal disease is challenged by the radiation tolerance of the normal liver parenchyma. A dosimetry guided combined approach that exploits complementary advantages of internal and external radiation delivery can be expected to improve treatment of HCC. To make this transition, however, prospective clinical trials establishing safety are needed. Furthermore, for routine clinic use, accurate and fast voxel-level dose estimation in internal radionuclide therapy, that lags behind external beam therapy dosimetry, is still needed. Our long-term goal is to improve the efficacy of radiation therapy with personalized dosimetry guided treatment. Our objective in this application is to demonstrate that it is possible to use 90Y imaging based absorbed dose estimates after SIRT to safely deliver external radiation to target regions (voxels) that are predicted to be underdosed and to develop deep learning based tools to make voxel-level internal dose estimation practical for routine clinic use. Specifically, in Aim 1, we will perform a Phase 1 clinical trial in HCC patients where we will take the novel approach of using the 90Y PET/CT derived absorbed dose map after SIRT to deliver SBRT to tumor regions predicted to be underdosed based on previously established dose-response models. The primary objective of the trial is to obtain estimates of safety of combined SIRT+SBRT for future Phase II trial design. In parallel, in Aim 2, building on promising initial results we will develop novel deep learning based tools for 90Y PET/CT and SPECT/CT reconstruction, joint reconstruction-segmentation and scatter estimation under the low count-rate setting, typical for 90Y. These methods have a physics/mathematics foundation, where convolutional neural networks (CNNs) are included within the iterative reconstruction process, instead of post-reconstruction denoising. In Aim 3, we will develop a CNN for fast voxel-level dosimetry and combine with the CNNs of Aim 2 to develop an innovative end-to-end framework with unified dosimetry-task based training. At the end of this study, we will be ready to use the new deep learning tools in a Phase II trial to demonstrate enhanced efficacy with SIRT+SBRT compared with SIRT alone and advance towards our long- term goal. This will accelerate adoption of these next-generation tools in clinical practice and will have a significant positive impact because treatment based on patient specific dosimetry will substantially improve efficacy, compared with current standard practice in SIRT. Although we focus on 90Y SIRT, our tools will be applicable in radionuclide therapy in general, a rapidly advancing treatment option.


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 = $0 )
2025	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	8	4/17/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $601,497 )
2023	2023	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	8	5/22/2023	NON-COMPETING CONTINUATION	$684,301
2023	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON STREET	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	7	2/9/2023	SUPPLEMENT FOR EXPANSION	-$82,804
														Subtotal = $601,497

Issue Date FY: 2022 ( Subtotal = $755,086 )
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	7	7/20/2022	NON-COMPETING CONTINUATION	$672,282
2022	2022	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	7	7/21/2022	SUPPLEMENT FOR EXPANSION	$82,804
														Subtotal = $755,086

Issue Date FY: 2021 ( Subtotal = $740,429 )
2021	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	6	5/26/2021	NON-COMPETING CONTINUATION	$0
2021	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	6	8/2/2021	SUPPLEMENT FOR EXPANSION	$82,804
2021	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	004	6	8/13/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2021	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	6	5/17/2021	NON-COMPETING CONTINUATION	$657,625
2021	2019	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	4/9/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $740,429

Issue Date FY: 2020 ( Subtotal = $670,584 )
2020	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	5	6/30/2020	COMPETING CONTINUATION	$670,584
														Subtotal = $670,584

Issue Date FY: 2019 ( Subtotal = $460,713 )
2019	2019	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	6/19/2019	NON-COMPETING CONTINUATION	$460,713
2019	2018	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	10/23/2018	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $460,713

Issue Date FY: 2018 ( Subtotal = $561,913 )
2018	2018	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	6/15/2018	NON-COMPETING CONTINUATION	$459,820
2018	2018	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	9/11/2018	SUPPLEMENT FOR EXPANSION	$102,093
														Subtotal = $561,913

Issue Date FY: 2017 ( Subtotal = $459,820 )
2017	2017	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	5/30/2017	NON-COMPETING CONTINUATION	$459,820
														Subtotal = $459,820

Issue Date FY: 2016 ( Subtotal = $461,991 )
2016	2016	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	9/14/2016	NEW	$461,991
														Subtotal = $461,991

Grand Total All Awards = $4,712,033

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Imaging and Dosimetry of Yttrium-90 for Personalized Cancer Treatment

Award Number: R01EB022075

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: 09/15/2016

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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