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

> **NIH NIH R01** · NORTHEASTERN UNIVERSITY · 2024 · $576,034

## Abstract

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.

## Key facts

- **NIH application ID:** 10784709
- **Project number:** 5R01CA260202-03
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** Mark Jonathan Niedre
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $576,034
- **Award type:** 5
- **Project period:** 2022-03-03 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10784709

## Citation

> US National Institutes of Health, RePORTER application 10784709, Continuous, Non-Invasive Optical Monitoring of Circulating Tumor Cell-Mediated Metastasis in Awake Mice (5R01CA260202-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10784709. Licensed CC0.

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