Wednesday, November 19, 2025 11/19/2025

Continuous, Non-Invasive Optical Monitoring of Circulating Tumor Cell-Mediated Metastasis in Awake Mice

Award Number: R01CA260202
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/03/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Continuous, Non-Invasive Optical Monitoring of Circulating Tumor Cell-Mediated Metastasis in Awake Mice - Project Summary Hematogenous metastasis is responsible for a large majority of cancer-related deaths, where circulating tumor cells (CTCs) shed from the primary tumor into the peripheral blood (PB). A small number of CTCs may form secondary sites, which are extremely difficult to control clinically. Most methods for studying CTCs rely on drawing and analyzing fractionally small PB blood samples (“liquid biopsy”). Although CTCs and multicellular CTC clusters (CTCCs) have been studied for decades, little is known about their “dynamics” in vivo (transient changes in their numbers in PB), and how these may affect metastasis development and response to anti-cancer treatment. For example, it is know that radiation therapy may encourage metastatic dissemination of cancer, yet the mechanisms for this are still poorly understood. Our team recently developed a new method for in vivo enumeration of CTCs in small animals called “diffuse in vivo flow cytometry” (DiFC). DiFC uses diffuse light to detect fluorescent-protein expressing CTCs in large, deeply-seated blood vessels. DiFC can sample approximately 100 microliters of blood per minute, permitting detection of fewer than 1 CTC per mL of PB, and sampling of the entire peripheral blood volume in minutes. We previously used DiFC to study rare CTC and CTCC dissemination in mouse xenograft models. DiFC revealed that CTC numbers are highly dynamic and may change by an order-of-magnitude or more over 24 hour periods. These changes are largely missed by CTC enumeration methods that involve infrequent blood draws. The goal of this project is to build a “wearable” tethered w-DiFC instrument that will allow continuous, non- invasive monitoring of CTC numbers over extended periods in mice. The w-DiFC optical probe and signal processing design will permit data collection in freely-moving mice in ambient lighting conditions. We will first use w-DiFC to study CTC dynamics during disease development in an orthotopic xenograft and transgenic mouse model of metastasis. We will use also w-DiFC to measure continuous CTC dynamics after radiation therapy in a medulloblastoma (MB) mouse model. MB is a common form of childhood brain cancer that aggressively metastasizes to the leptomeningeal surfaces of the brain and spine via the PB. There is significant evidence that radiation may exacerbate metastasis by triggering mobilization of CTCs into the blood. We expect that the ability of w-DiFC to measure CTCs over short-, medium-, and long-term timescales will provide unique insights into this process. We will also use w-DiFC to study the use of anti-inflammatory drugs to block the pro-metastatic effect. Hence, the studies proposed here could ultimately lead to better understanding of metastasis and improved treatment protocols for childhood MB. We anticipate that the unique technologies that will be developed here will have broad application to other cancers and anti-cancer therapies in the future.


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 = $580,950 )
2025	2025	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	4	2/19/2025	NON-COMPETING CONTINUATION	$522,857
2025	2025	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	4	9/15/2025	NON-COMPETING CONTINUATION	$58,093
														Subtotal = $580,950

Issue Date FY: 2024 ( Subtotal = $576,034 )
2024	2024	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	3	1/24/2024	NON-COMPETING CONTINUATION	$545,716
2024	2024	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	3	4/16/2024	NON-COMPETING CONTINUATION	$30,318
														Subtotal = $576,034

Issue Date FY: 2023 ( Subtotal = $519,595 )
2023	2023	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	2	2/13/2023	NON-COMPETING CONTINUATION	$519,595
														Subtotal = $519,595

Issue Date FY: 2022 ( Subtotal = $441,188 )
2022	2022	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	1	3/3/2022	NEW	$441,188
														Subtotal = $441,188

Grand Total All Awards = $2,117,767

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Continuous, Non-Invasive Optical Monitoring of Circulating Tumor Cell-Mediated Metastasis in Awake Mice

Award Number: R01CA260202

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/03/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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