Development of next-generation targeted MRI contrast agents - the objective of this research project is to develop the next generation of safe and effective MRI contrast agents for accurate and…

The National Institutes of Health National Cancer Institute awarded Molecular Theranostics LLC $528,259 on September 1, 2026, under the Cancer Detection and Diagnosis Research program (CFDA 93.394) to develop next-generation targeted MRI contrast agents for cancer detection and diagnosis.

The recipient will design, synthesize, and optimize targeted gadolinium- and manganese-based MRI contrast agents using PYCLEN chelating ligands. The work addresses safety concerns associated with current clinical gadolinium-based contrast agents, particularly gadolinium ion retention in tissues and adverse reactions in patients with impaired kidney function. The project builds on the recipient's development of MT218, a first-in-class targeted MRI contrast agent specific to extradomain-B fibronectin in tumor extracellular matrix that has demonstrated an excellent safety profile in preclinical assessments and early-phase clinical trials. The next-generation agents will incorporate manganese chelates as non-gadolinium alternatives and high-relaxivity gadolinium chelates to minimize gadolinium dose delivered to patients while maintaining or improving diagnostic sensitivity for solid tumors.

Place of performance is Ohio, USA. The period of performance runs from September 1, 2026, through August 31, 2031. Molecular Theranostics is a small, disadvantaged business and Asian-Pacific American owned limited liability company registered in SAM.gov. The award is structured as a Project Grant, the standard assistance type for NIH research funding.

Development of next-generation targeted MRI contrast agents - the objective of this research project is to develop the next generation of safe and effective MRI contrast agents for accurate and sensitive detection and diagnosis of cancer to improve the clinical management of the disease. MRI remains one of the most commonly used imaging modalities for cancer diagnosis and treatment planning. However, all clinical gadolinium (GD)-based contrast agents (GBCAS) remain untargeted, have seen little improvement in cancer diagnosis, and have long-standing safety concerns surrounding gadolinium ION retention in tissues and adverse reactions in patients with impaired kidney function. We have recently developed the first-in-class targeted MRI contrast agent MT218 specific to extradomain-B fibronectin in the tumor extracellular matrix for high-resolution molecular imaging of solid tumors with MRI. MT218 has shown excellent safety profile in preclinical assessments and early phase clinical trials. Recently, pyclen based macrocyclic chelating ligands have been used for both manganese (MN) and GD ions to develop next- generation contrast agents with high stability. MN-pyclen chelates demonstrate relaxivity similar to other clinical GBCAS and have great potential as non-GD MRI contrast agents. GD-pyclen chelates, including the recently FDA-approved gadopiclenol, demonstrate relaxivity far superior to other GBCAS and offer the ability to significantly reduce the gadolinium dose delivered to patients. In this project, we propose to design and develop the next generation of targeted MRI contrast agents using MN and GD chelates of pyclen derivatives to address the safety concerns related to GBCAS. The specific aims of this project are 1) to design, synthesize, and optimize the next-generation of targeted GD-based contrast agent with high relaxivity to minimize their potential dose-dependent toxicity as well as targeted MN-based contrast agents as non-GD alternatives for high-resolution MR molecular imaging of cancer; 2) to evaluate the efficacy of the targeted contrast agents for cancer detection and characterization in mouse xenograft and allograft tumor models; 3) to perform comprehensive preclinical assessments of the lead targeted contrast agents in animal models, including pharmacokinetics, tumor targeting, biodistribution, clearance, in vivo stability, and safety. The novel targeted contrast agents have the potential to address the safety concerns of the existing agents for broad clinical applications, ultimately having a significant impact on decision-making in cancer management and improving healthcare of cancer patients.