# Chelator development for improved scandium theranostic agents

> **NIH NIH SC2** · HERBERT H. LEHMAN COLLEGE · 2020 · $165,000

## Abstract

Project Summary/Abstract
Scandium-44 (44Sc) is a positron emitting radionuclide with a half-life of 3.97 h that is well-suited for use in
positron emission tomography (PET) imaging. Scandium-47 (47Sc) is a beta emitter with a half-life of 3.345 d
appropriate for targeted radiotherapy. When combined, 44Sc and 47Sc present an ideal radioisotope pair for use
in theranostic agents meant to both diagnosis and treat disease. As radiometals, both isotopes of Sc require
the use of a bifunctional chelator to attach the radioactive metal cation to a targeting vector that dictates the
specific localization of the drug conjugate. Since 44Sc and 47Sc are both up and coming radionuclides for
medical applications, there is a need for further chelator development for Sc-based radiopharmaceuticals. The
most widely used chelator for Sc(III) is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA);
however as a macrocylic chelator, DOTA requires harsh radiolabeling conditions (high temperatures and long
reaction times) to form the Sc-DOTA complex that are incompatible with sensitive biological molecules often
used as targeting vectors in the drug conjugates. This research aims to investigate and develop an acyclic
chelator for stably complexing Sc(III) under biologically compatible radiolabeling conditions to facilitate the use
of Sc radioisotopes in targeted radiopharmaceuticals.
To achieve these goals, this proposal aims to investigate the chelation chemistry of Sc(III) through the
synthesis of small peptides as model systems to probe the effects of denticity, cavity size, and binding moiety
on chelate stability, both experimentally and computationally. A series of tripeptides and tetrapeptides
comprised of natural and non-natural amino acids will be synthesized and complexed with non-radioactive
Sc(III). Selected Sc-peptide complexes will be further studied using density functional theory (DFT) calculations
to probe the structure and geometry of the complexes. The trends observed with the peptide systems will
inform the selection of promising acyclic chelators to be complexed with non-radioactive Sc and radioactive
44Sc. The acyclic chelators will be assessed based on their ability to readily chelate Sc under mild conditions
with high purity, and on complex stability. The lead radiolabeled Sc-chelates will then be evaluated in vivo in
mouse models through a collaboration with Memorial Sloan Kettering Cancer Center. PET imaging and
biodistribution studies will be carried out to determine the in vivo stability and utility of the acyclic chelators in
comparison with the current gold standard DOTA chelator. 44Sc-chelator complexes will be studied in healthy
mice while 44Sc-chelator-octreotate (Y3-TATE) bioconjugates will be studied in tumor-bearing mice to monitor
targeting to the somatostatin subtype 2 receptor (SSTr2) that are upregulated in neuroendocrine tumors. The
development of acyclic chelators for rapid complexation of Sc radionuclides under mild ...

## Key facts

- **NIH application ID:** 9888372
- **Project number:** 5SC2GM130464-02
- **Recipient organization:** HERBERT H. LEHMAN COLLEGE
- **Principal Investigator:** Melissa A Deri
- **Activity code:** SC2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $165,000
- **Award type:** 5
- **Project period:** 2019-03-06 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888372

## Citation

> US National Institutes of Health, RePORTER application 9888372, Chelator development for improved scandium theranostic agents (5SC2GM130464-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9888372. Licensed CC0.

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