The major focus of research in the Rogers lab is the radiolabeling of proteins and peptides with various radioactive metals for PET imaging (Cu-64, Ga-68, Zr-89, Y-86) and therapy (Y-90, Lu-177, I-131, potential alpha-emitters).
Peptides
The main targets have been the somatostatin receptor subtype 2 (SSTR2) and the gastrin-releasing peptide receptor (GRPR) that are overexpressed on neuroendocrine, prostate and breast cancers. Analogs of the eight amino acid peptide, octreotide, are generally used for targeting SSTR2, while analogs of the fourteen amino acid bombesin peptide are generally used for targeting GRPR. These peptides are conjugated with bifunctional chelators for complexing various radioactive metals.
Antibodies
We are working with Dr. Farrokh Dehdashti, MD (Department of Radiology) on the Zr-89 labeling of the anti-HER2 antibody, trastuzumab for a clinical trial. The ultimate goal of this study is to demonstrate that 89Zr-trastuzumab-PET will assist in identifying patients with HER2-positive breast cancer likely to be resistant to HER2-targeted therapy.
Alzheimer’s disease (AD)
We are collaborating with Dr. Liviu Mirica, PhD (Department of Chemistry) on the development of metal-containing compounds for PET imaging of Ab aggregates, including soluble Ab oligomers, as an early diagnostic tool for AD. The working hypothesis here is that bifunctional chelators that bind transition metal ions very tightly and have a high affinity for Ab species, including soluble Ab oligomers, could be used as PET imaging agents for early AD diagnosis. We postulate based on preliminary data that these bifunctional chelators can be efficiently radiolabeled with the 64Cu radionuclide – a longer-lived ideal PET tracer, bind to different amyloid aggregates, and thus act as novel diagnostic agents for AD.
Bacterial infection imaging
In collaboration with Dr. Paul Savage, PhD (Department of Chemistry, Brigham Young University) we are developing PET imaging agents based on a novel class of antimicrobial agents for the specific detection of bacterial infections.
These novel antimicrobial agents are cationic steroid compounds, designed to mimic the morphology of endogenous antimicrobial peptides and have been shown to be effective against both Gram-positive and Gram-negative bacteria.
These compounds display high and selective affinity for bacterial membranes over eukaryotic cells. In these studies, we will modify the cationic steroid antibiotics (CSAs) with the 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) chelator such that they can be radiolabeled with the positron-emitter, 64Cu.
Single-chain variable antibodies (scFvs)
We are isolating scFvs against a variety of cancer relevant targets from a commercial phage display library. These scFvs will be formatted into a different antibody constructs (diabody, scFv-Fc, etc.) and radiolabeled with different radioactive metals to determine target-specific binding both in vitro and in vivo. In addition, we are constructing our own library that will ultimately give more flexibility when identifying scFvs.