Targeted Molecular Imaging Agents – Lighting up Cancer Cells
Hans Schmitthenner (School of Chemistry and Materials Science)
The philosophy in the Schmitthenner lab is to apply fundamental aspects of chemistry and imaging science to practical applications in medical imaging and cancer research. Our research involvers a mix of peptide, dye and organometallic chemistry combined with fluorescence, photoacoustic, MRI and PET imaging.
Our goal is to transform screening and early diagnosis of cancer by creating novel imaging agents that specifically target cancer cells. Our strategy incorporates new synthetic methods which we developed at RIT for preparing single and multi-modal imaging agents. These agents are built on a modular peptide scaffold with features that facilitate their gentle conjugation to biomolecules that target cancer cells. This conjugation is performed in the last step which broadens the utility of imaging agents for a wide variety of cancers and other diseases by simply changing the targeting agent.
In collaboration with Dr. Irene Evans (SOLS) we were able to evaluate our TMIA’s by staining and imaging human lung cancer A549 cells and prostate cancer C4-2B cells by confocal fluorescence microscopy (CFM). Utilizing the near infrared (NIR) fluorescence we were able to selectively light up the cancer cells by the use of selective targeted imaging agents (TMIA’s) and show an important utility for the new CFM within the College of Science.
In collaboration with Dr. Joseph Hornak (CIS and SCMS) a method was also developed to measure of T1 relaxation times in NMR. This is a measure of the efficacy of gadolinium containing agents in magnetic resonance imaging. We have made dual modal agents containing a dye for CFM and gadolinium for MRI using our modular method.
We have further developed a practical method for transmetalation of imaging agents for PET imaging based on the exchange of a placeholder metal which serves as a protecting group during synthesis. This includes the preparation of targeted agent with targeting group and place-holder metal which may be exchanged in the clinic or facility that can exchange the placeholder for a radioactive metal for PET imaging. This is significant as it affords a rapid and safe method to prepare radioactive PET agents.
Two US patent application which includes students as inventors have been filed. The first is based on the truly modular approach which can be used to place multiple imaging agents of one type (single modal) or more than one type (dual or multi-modal) on a single template. The second is a method to synthesize radioactive PET agents from non-radioactive single or dual-modal imaging agents for PET-NIR or PET-MRI using the transmetalation method.
With a third collaborator, Dr. Navalgund Rao (Center for Imaging Science our group recently received an NIH R15 area grant that builds on these advances coupled with advances made in instrumentation for photoacoustic imaging (PAI) of prostate cancer (PrCa). A research collaboration was then forged between researchers at the Rochester Institute of Technology (RIT) and a team of cancer biologists and radiologists at Roswell Park Cancer Institute with the goal of developing a new screen for prostate cancer.