# PET Imaging Agents for Protoporphyrin IX

> **NIH NIH R21** · EMORY UNIVERSITY · 2022 · $215,101

## Abstract

Project Summary
 Primary brain tumor is a major central nervous system malignancy with 23,800 estimated total new
cases in the US in 2017 resulting in 16,700 deaths. High grade glioblastomas (HGG; WHO grades III and IV) in
particular carry a dismal prognosis. Glioblastomas are known for their molecular and cellular heterogeneity
which contributes to the highly aggressive malignant behaviors of tumor cells, including high proliferation,
infiltration and development of resistance to treatment. Therefore, non-invasive imaging approaches that can
provide molecular and metabolic information of the glioblastomas are important to characterize a specific tumor
for subtype specific and individualized treatments. As a non-invasive clinical imaging modality, positron
emission tomography (PET) is capable of molecular and metabolic imaging applications, however, its
application in brain tumor is limited. The clinical standard of fluorodeoxyglucose (FDG) PET has low specificity
and is not appropriate for brain tumor imaging given the high FDG uptake in normal brain tissue. Currently,
there is a significant unmet need in molecular imaging probes for imaging highly heterogeneous and infiltrating
gliomas. The overall objective of this exploratory project is to develop a fluorine-18 labeled analog of 5-
aminolevulinic acid (5-ALA), which is an FDA approved imaging tracer for intraoperative imaging of gliomas, to
provide molecular and metabolic information of the glioma. This innovative new PET imaging capability can be
used to characterize a tumor for subtype specific diagnosis and clinical decisions on individualized treatments
as well as monitoring the treatment responses. The central hypothesis of this proposal is that a fluorine-18
labeled 5-ALA will enable PET imaging for glioma metabolism and activity on tumorigenicity and cellular
proliferation based upon tumor cell metabolizing 5-ALA to produce protoporphyrin IX in highly heterogeneous
and infiltrating gliomas. This hypothesis and scientific premise of the project are supported by our preliminary
findings that: 1) in vivo pre-clinical PET evaluation of 13N-5-ALA with rats bearing intracranial 9L gliomas
demonstrated highly selective uptake of 13N-5-ALA within the tumor, and tumor specific contrast without
background; 2) racemic 3-fluoro-5-ALA shows greater substrate reactivity for protoporphyrin IX synthesis in
glioma cells than 5-ALA. Thus, our exploratory development of this novel PET tracer for brain tumor imaging
will focus on the following specific aims: 1. to synthesize and in vitro characterize R- and S-3-fluoro-5-ALA; 2.
to develop radiolabeling methods for the candidate R- and S-3-[18F] fluoro-5-ALA ligands; and 3. to determine
whether developed R- and S-3-[18F] fluoro-5-ALA ligand candidates can be selectively taken up in the
intracranial tumors in rodent orthotopic models of glioblastomas.

## Key facts

- **NIH application ID:** 10330484
- **Project number:** 5R21CA259935-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Mark Myron Goodman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $215,101
- **Award type:** 5
- **Project period:** 2021-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330484

## Citation

> US National Institutes of Health, RePORTER application 10330484, PET Imaging Agents for Protoporphyrin IX (5R21CA259935-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10330484. Licensed CC0.

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