# Multicolor PET to interrogate cancer biology

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $627,848

## Abstract

SUMMARY: The problem: In molecular medicine multiple parameters are combined for a more inclusive
evaluation towards personalized medicine. A thorough characterization of a patient’s tumor upfront provides
better outcomes, i.e., better insight affords higher survival rates. In contrast and almost anachronistically, PET
imaging (the most sensitive and quantitative imaging method) is “monochromatic” as it can only assess one
parameter at the time, lacking depth of information. Suitable imaging tools that allow visualization of more than
one target in patients are needed, akin an in vivo cytometry. Optical imaging utilizes multiple parts of the
spectrum to visualize several targets simultaneously, but this is not feasible for whole-body clinical imaging due
to the limited penetration of light. Single-photon emission computed tomography (SPECT) can distinguish
several isotopes based on the energy of their emissions, but spectra often overlap and the required collimation
significantly decreases sensitivity. Different tracers could be imaged sequentially with PET but multiple scans
increase the dose exposure from the required CT scans. It also requires sufficient decay of one tracer over time
to be able to image the remaining one, decreasing convenience for patients. For three or four different isotopes
this requires an even more complex coordination. As a solution, we propose the new modality of multicolor PET
(mPET), which allows for simultaneous PET acquisitions of up to four different radiotracers at the same time.
This new imaging paradigm utilizes one standard (pure) positron emitter together with positron-gamma emitters
that produce triple (positron-gamma) coincidences, where a prompt gamma emission immediately follows the
positron and identifies the isotope. We already imaged two isotopes in a standard PET scanner with the aid of
the additional gamma signal but without energy discrimination. Here, we utilize the energy of the gamma signal
as “barcode identifier” for the corresponding isotope while the spatial information is carried with the 511 keV
annihilation photons. The prompt gamma requires detection without spatial decoding, which is achieved by an
add-on gamma detector with sufficient energy discrimination and temporal resolution that is synchronized with
the PET scanner. We established this system already and imaged three isotopes together. Here, we will in Aim
1 optimize the mPET set-up and then employ mPET to address important clinical/biological problems: In Aim 2,
we will dissect the tumor microenvironment, interrogating signatures important for prognosis. In Aim 3, we will
use mPET to interrogate important players in checkpoint inhibition therapy (CD4+ / CD8+ / PD-L1 /
macrophages) simultaneously over time to predict response and will explore cellular therapies by following the
injected cells to their target. The overall impact of this study will be significant, as mPET represents a true
paradigm shift, allowing imaging of several ...

## Key facts

- **NIH application ID:** 10829377
- **Project number:** 5R01EB033000-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Jan Grimm
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $627,848
- **Award type:** 5
- **Project period:** 2023-05-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829377

## Citation

> US National Institutes of Health, RePORTER application 10829377, Multicolor PET to interrogate cancer biology (5R01EB033000-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10829377. Licensed CC0.

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