Barry Shulkin, MD

The use of radioactive materials in the diagnosis, treatment, and surveillance of certain cancers has been significantly impactful. Radioactive isotopes, or radioisotopes, that are created from charged particle nuclear reactions can be coupled with biologically relevant compounds to create radiotracers. Radiotracers take advantage of the aberrant metabolism of tumor cells or specific binding interactions in the tumor microenvironment. The resulting accumulation of radioactivity can then be imaged with techniques like positron emission tomography (PET) with or without computed tomography (PET-CT), providing a highly specific and sensitive picture of the tumor and its environment. 

One of the most useful radiotracers available is 2-deoxy-2-[¹⁸F]-fluoro-D-glucose, or [¹⁸F]FDG. This glucose analog is easily transported across the cell membrane by metabolically hyperactive tumor cells and is phosphorylated to FDG-6-phosphate. Unlike glucose-6-phosphate, FDG-6-phosphate cannot be used as a substrate for glycolysis, thereby allowing for its accumulation in the tissue (except in the liver). This radiotracer can be used to assess hypermetabolic tumors and provides highly sensitive data pertaining to the diagnosis, staging of tumors, and response to treatment. We assist in the utilization of this radiotracer for our patient population in preclinical studies and clinical trials.  

For neuroendocrine tumors like neuroblastoma, we can use a radiotracer called ¹²³I-metaiodobenzylguanidine (mIBG), or ¹²³I-MIBG. This norepinephrine analog is taken into neuroendocrine cells and stored in neurosecretory granules. The resulting radioactive accumulation provides high contrast images of tumor cells compared to healthy tissue. This radiotracer is considered a diagnostic imaging agent whereas ¹³¹I-MIBG can be used as a therapeutic agent due to the higher dose of radiation it possesses. 

Other pediatric brain tumors can be assessed with ¹¹C-methionine, or ¹¹C-Met. This amino acid tracer has produced highly sensitive and accurate images when used for analysis of pediatric central nervous system tumors, specifically when recurrence is suspected. Our studies have shown that ¹¹C-Met PET precisely differentiates between novel tumorigenesis and treatment-related effects and has predictive power when determining overall survival. 

I am also interested in identifying novel applications for nuclear medicine in our pediatric population. For example, many children with sickle cell disease go on to develop cardiac issues. We are applying the use of radiotracers to myocardial perfusion imaging tests to determine the extent of any cardiac damage caused by the disease. Additionally, we are optimizing a nuclear medicine-based approach to help stratify patients based on their risk for cardiac disease.