# Development of Gd(III)-Pt(II) MR Probes for Tandem Detection & Chemotherapy

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2021 · $32,248

## Abstract

Cisplatin is one of the most widely used chemotherapeutics for solid tumors. Despite its clinical utility,
cisplatin suffers from significant off target toxicity. Additionally, it is susceptible to chemoresistance through
several mechanisms, most commonly by decreased accumulation. Patients prescribed cisplatin typically
undergo two cycles of therapy (six weeks total) before the tumor is reevaluated for a response. During this time,
patients are exposed to significant toxicity without knowing if the treatment is effective. Furthermore, if the tumor
does not respond to cisplatin, a crucial period of time has been wasted when a more effective treatment could
have been prescribed instead. If there were a tool that could predict whether or not a tumor will respond to Pt(II)
chemotherapy, it could mitigate patient exposure to harmful side effects and help ensure the best treatment
option is prescribed. Currently, there is no such tool, which makes this issue a critical unmet need in medicine.
 Clinically approved Gd(III) MR contrast agents (CAs) provide a versatile platform for developing Gd(III)-
Pt(II) theranostic agents that can predict if tumors are susceptible to Pt(II) chemotherapy and provide
simultaneous anti-cancer therapy and detection through MR imaging. The Meade lab is a pioneer in the
development of bioresponsive Gd(III) MR CAs that “turn on” by an increase in relaxivity through modulation of
one or more inner sphere parameters. One such parameter is 𝜏R, the rotational correlation time. A large increase
in 𝜏R, which occurs when CAs bind to large biomolecules, results in a drastic increase in relaxivity, which is seen
as brighter contrast in an MR image. By coordinating a cis-dichloroplatinum(II) moiety to Gd(III) CAs, the resulting
Gd(III)-Pt(II) compounds will mimic cisplatin. As such, the agents can bind DNA, giving them anti-cancer
properties and increasing the relaxivity for brighter MR contrast. The change in relaxivity occurs only when DNA
is bound, therefore these agents can be used to predict whether or not tumors of interest are susceptible to
treatment with cisplatin. If no contrast increase is observed, the agents were not able to enter the cells and bind
DNA, therefore the tumor likely will not respond to therapy. All agents synthesized will be tested in vitro in cisplatin
sensitive and resistant cell lines and MR images will be obtained. The agents will be screened in an additional
50+ breast cancer cell lines in the laboratory of Professor Dai Horiuchi at Northwestern. The agents will also be
tested in vivo in murine models with cisplatin sensitive and resistant flank xenografts.
 This proposed project adheres to the mission statement and funding plans of the NIH. The research
seeks to develop novel molecular imaging probes as tools to predict tumor response to cisplatin therapy and
then provide simultaneous anti-cancer therapy and monitoring by MR imaging. Currently, there is no effective
way to predict if a tumor will res...

## Key facts

- **NIH application ID:** 10149970
- **Project number:** 5F31CA239426-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Casey Adams
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $32,248
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149970

## Citation

> US National Institutes of Health, RePORTER application 10149970, Development of Gd(III)-Pt(II) MR Probes for Tandem Detection & Chemotherapy (5F31CA239426-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10149970. Licensed CC0.

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