# Development of Superior Chelation Chemistry for 89Zr-ImmunoPET Imaging

> **NIH NIH R01** · ILLINOIS INSTITUTE OF TECHNOLOGY · 2020 · $403,933

## Abstract

ABSTRACT
Positron emission tomography (PET) is a sensitive and non-invasive imaging technique applicable to diagnosis
and staging of various diseases. Research efforts have been devoted to develop tumor-specific PET imaging
probes. Zirconium-89 (89Zr, t1/2 = 78 h) is a positron-emitting radionuclide suitable for targeted PET imaging of
tumors using an antibody with a relatively long biological half-life.
89Zr is known to display a high binding affinity for bone mineral, hydroxylapatite (HA). Premature release of 89Zr
from 89Zr-based biomolecules during clinical PET imaging can lead to high accumulation of radioactivity in bone
and generate radiation toxicity including bone marrow toxicity. Less stable 89Zr-labeled PET tracers also result
in diminished image quality and inaccurate dosimetry. Therefore, a stable 89Zr-complex using an optimal chelator
should be employed for safe and sensitive immuno-PET imaging. Such an effective chelator is also required for
practical labeling of a temperature-sensitive antibody with highly energetic 89Zr under mild reaction conditions to
minimize radiolytic damage resulting from extended exposure of the antibody.
Clinical potential of 89Zr-radiopharmaceuticals for PET imaging of cancers has been well demonstrated in
numerous preclinical and clinical trials. While DFO (desferrioxamine B) is currently used as the standard for
chelation of 89Zr, DFO-antibody conjugates labeled with 89Zr have limited in vivo stability resulting in high
accumulation in normal organs and tissues, including bone.
The objective of this investigation is to create fluorescent novel chelators of 89Zr built on the structurally unique
coordinating groups and chelation chemistry that the PI invented. Innovative aspects of this investigation include
i) development of new small molecule donors with high binding affinity for 89Zr and ii) construction of new ligand
platforms that can form a highly stable complex with 89Zr and iii) application of novel self-fluorescent chelators
for in situ analysis of unbound 89Zr and bound 89Zr complexes.
Specific aims of this proposal are i) rational design of novel chelation chemistry with high affinity for 89Zr(IV); ii)
library synthesis of the new chelators with structural variations; iii) evaluation of new chelators for radiolabeling
kinetics and complex stability with 89Zr and spectrophotometric and fluorescent analysis of 89Zr complexes; iv)
selection and conjugation of the best (see above criteria) chelators to a model antibody; v) biodistribution,
pharmacokinetics, metabolism, and PET imaging studies of the best chelator-antibody conjugates using tumor
bearing mice. Completion of this study is proposed to materialize superior 89Zr chelation chemistry that will
contribute to development of clinically viable PET tracers for sensitive and safe imaging of various diseases and
accurate dosimetry of targeted radiotherapy using different α- or β--emitting radionuclides.

## Key facts

- **NIH application ID:** 10073381
- **Project number:** 1R01EB029800-01A1
- **Recipient organization:** ILLINOIS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** HYUN-SOON CHONG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,933
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073381

## Citation

> US National Institutes of Health, RePORTER application 10073381, Development of Superior Chelation Chemistry for 89Zr-ImmunoPET Imaging (1R01EB029800-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10073381. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*