I-Corps: CardioTrak: Using Cardiac Targeting Peptide to Image the Heart

University Of Pittsburgh, Pittsburgh PA

Investigators

Abstract

The broader impact/commercial potential of this i-Corps project would be the ability to bring to market a heart-targeted radioisotope for use during stress testing. This is a field that has not seen any new imaging agents come to market in ~25 years. Current stress tests rely on a particular formulation of Technetium, a radioisotope, to image the heart at rest and at peak stress. This current clinical standard, Technetium Sestamibi, goes to multiple organs other than the heart leading to poor image quality due to high signal to noise ratio as well as increasing radiation exposure. By using a Cardiac Targeting Peptide (CTP) we can target the radiation to only where it is needed for imaging, thereby improving image quality, reducing false positive results and decreasing radiation exposure by as much as 80%. We have chosen a radioisotope as our first cargo due to the widespread use of stress testing contributing to the highest radiation exposure in medical care, and due to a reasonable length of time/expense to FDA approval. This is scratching the surface of CTP's potential and once we can provide proof of concept in the human imaging application, the path will open for multiple other applications. This I-Corps project is based on a novel, non-naturally occurring, 12-amino acid cell penetrating peptide that we termed Cardiac Targeting Peptide or CTP due to its ability to enter heart cells after a peripheral intravenous injection. Both cardiac diagnostics and therapeutics suffer from a lack of vectors specifically targeting the heart. Our work utilizing phage display identified CTP which we believe is a viable solution. In our biodistribution studies, the peak uptake occurred at 15 mins, illustrating that CTP would be a useful vector in acute cardiac conditions like myocardial infarction in which the window of opportunity is limited to ~6 hours. We were able to show this targeting activity in mouse heart, ex-vivo explanted human heart tissue from patients undergoing heart transplants and in human induced pluripotent stem cell derived cardiomyocytes, demonstrating that CTPs ability to enter heart cells is not species limited and has human applicability. We have labeled CTP with a radioisotope, Technetium 99m, using a chelator Hydrazinonicotinamide and delivered the radiation to the heart with minimal or no uptake by other organs. We have also demonstrated that CTP is able to internalize bigger cargo into heart cells like the biotin-streptavidin complex. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.