Development of theranostic ligands and targeted radiotherapeutics

Completed Research Project
James Kelly, Ph.D.
Last Updated: 
June 14, 2022

In work that has been collectively recognized by the European Association of Nuclear Medicine in the form of a Young Investigator Award, and by the Society of Nuclear Medicine and Molecular Imaging in the form of an Alavi-Mandell Award, Dr. Kelly has exploited serum albumin as a method of modifying the pharmacokinetics of small molecule prostate specific membrane antigen (PSMA) ligands, thereby creating platforms of compounds for theranostic use. The first-generation platform consisted of radioiodinated dual-targeting ligands with affinity for PSMA and for serum albumin. Identification of an albumin-binding moiety with suitable affinity led to the creation of trifunctional ligands that can be labeled by radiometals for positron emission tomography (PET) imaging and/or targeted radiotherapy. To enhance the yield of the labeling reaction and improve the in vivo stability of the metal complex, Dr Kelly and collaborators designed and incorporated novel cyclic metal chelators with rapid labeling kinetics and high thermodynamic stability. These ligands, which have been labeled with 66/68Ga, 64/67Cu, 111In, 177Lu and 225Ac have achieved dramatic improvements in both total dose to tumors and tumor-to-kidney ratio. The most promising ligand to date, [225Ac]Ac-RPS-074, achieved a complete tumor response following a single administration to mice bearing LNCaP xenograft tumors. 

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065