# Cerenkov 2.0 – Cerenkov-activated agents for imaging and therapy

> **NIH NIH R56** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $716,758

## Abstract

SUMMARY. The problem: Cerenkov luminescence (CL) imaging (CLI) is a new imaging method that utilizes
light emitted during the decay of radiotracers. In contrast to fluorescence imaging, where currently only very few
agents are clinically available, CLI can tap into the wealth of clinically used specific radiotracers for optical
imaging, e.g. during surgery. We already have demonstrated pre-clinical CLI applications as well as clinical CLI.
Yet, due to its very low signal intensity the versatility of CL remains limited. Imaging requires strict exclusion of
ambient light, and CL-mediated photoactivation demands unrealistic high doses. Proposed solution: To
overcome these challenges, we hypothesized that we could (i) explore the short-wave infrared (SWIR) part of
the Cerenkov spectrum for CLI under ambient light (Aim 1); and (ii) utilize clinical radiotracers together with a
hallmark of cancer cells to activate a prodrug in tumors for a new therapy paradigm (Aim 2). We propose these
two independent specific aims: In Aim 1, we will explore SWIR CLI in the spectral range of 900-1300 nm. This
spectral range has the advantage of significantly reduced autofluorescence, absorption and scatter and provides
much higher depth penetration, yielding images with much higher contrast and resolution. There are no clinical
approved agents operating in this area. Theoretical prediction shows that the broad-spectrum CL should have
also a SWIR component (iCL). We now demonstrated that iCL can indeed be detected from clinical radiotracers
using specialized cameras. Considering that human eyes detect light from ca. 400 to 700 nm it will be feasible
to use non-SWIR emitting LED lightening, enabling iCL imaging (iCLI) to be carried out in a well-lit room without
any enclosure. This liberates CLI from the mandatory total darkness during imaging that required special
enclosures and limited further clinical applications. Aim 2 focuses around or radiotracer-activated prodrug
doxazolidine-borate that is only activated in tumors via reactive oxygen species (ROS). The ROS generated via
radiolysis from radiotracers will add to the already increased ROS levels present as cancer hallmark in tumors,
providing in combination a highly cancer-specific activation mechanism that spares normal cells that have
regulated ROS levels and only see background levels of the tracer. The high potency (IC50 of ~5 nM) makes
this an ideal agent to be activated by radiotracers, which are present only in very low amounts. By adding erastin
to further increases ROS, we can pharmacologically enhance the therapy. In addition, this approach could be
used for other drugs, e.g. to treat severe inflammatory diseases such as arthritis or vasculitis where anti-
inflammatory drugs further reduce the quality of life in these patients. Taken together, our work is not only moving
CL further into new realms but is also adding an entirely new imaging and therapy paradigm. This continuation
of our work is significant...

## Key facts

- **NIH application ID:** 10644155
- **Project number:** 1R56EB030512-01A1
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Jan Grimm
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $716,758
- **Award type:** 1
- **Project period:** 2022-09-15 → 2024-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10644155

## Citation

> US National Institutes of Health, RePORTER application 10644155, Cerenkov 2.0 – Cerenkov-activated agents for imaging and therapy (1R56EB030512-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10644155. Licensed CC0.

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