Development and evaluation of molecular 103PD auger electron radiopharmaceuticals

Active Project Grant Awarded Last action

Award ID
F32EB040380
Recipient
Awarding agency
Obligated
$76,780

Award facts

Assistance listing
93.286 Discovery and Applied Research for Technological Innovations to Improve Human Health
Completion date 0% complete
Place of performance
Madison, WI 53715, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The overarching scientific goal of this proposal is to develop chelators and strategies to enable the utilization of auger and conversion electron (ACE) emitters 103PD and decay daughter 103MRH in targeted radiotherapy (TRT). Recent first-in-class FDA-approved drugs utilize 177LU, a β- emitter, anchored to a targeting peptide for the treatment of metastatic prostate cancer. Use of a targeted 68GA diagnostic tool prior to treatment with therapeutic 177LU greatly improves treatment outcomes through a theranostic approach to disease treatment. Certain types of disease, such as micrometastatic cancer, are not amenable to β- therapy due to the low linear energy transfer (let) of this decay mode. Clinical trials using α particle emitters such as 225AC have demonstrated promising results, capitalizing range on the order of 5 cells compared to up to CA. 100 for β- emission. However, there are significant concerns regarding off-target toxicity due to highly destructive α particles, in addition to supply chain constrictions and regulatory hurdles. 103PD/103MRH emit low-energy x-rays and cascades of electrons (aces) through radioactive decay over an exceptionally narrow range less than the diameter of a single cell. Preclinical study of 103PD-based radiopharmaceuticals is stalled by the paucity of chelators suitable for PD and the absence of diagnostic tools due to the lack of imaging capability using 103PD decay emissions. The specific aims of this proposal seek to solve challenges through the lens of coordination chemistry. The aims include (1) development of a psma-targeted chelator suited for the 68GA/103PD theranostic pair, (2) radiofluorination for 18F/103PD "radiohybrid" theranostics, and (3) tuning cellular localization with organelle-specific targeting vectors. Supported by preliminary results indicating suitability of tetrahydrosalen ligands and their derivatives, and literature precedent for cyclam chelators, this proposal will create the chemical and diagnostic tools necessary for unleashing the potential of ACE therapy. Through the attached research training plan, the applicant will develop the necessary skills to lead biomedical research at the interface of inorganic chemistry and targeted radiotherapy through CO-sponsorship of profs. Jonathan engle (medical physics) and eszter boros (chemistry). Specifically, the applicant will address gaps in training by mastering radiochemistry, preclinical evaluation, and mammalian cell culture. In SUM, the applicant will develop critical tools for the study of novel ACE radiopharmaceuticals and their preclinical evaluation while taking advantage of the world-class facilities and professional development environment available to postdoctoral scholars at the university of wisconsin-madison.

Quick answers

Who received award F32EB040380?

F32EB040380 was awarded to University Of Wisconsin System by National Institute of Biomedical Imaging and Bioenginering (National Institutes of Health) on January 30, 2027.

How much is award F32EB040380 worth?

$76,780 has been obligated on F32EB040380.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login