Jason S. Lewis is Chief of the Radiochemistry Service, Associate Vice Chair of Basic Research, Chief and Associate Attending Radiochemist, and Director of the Cyclotron Core in the Department of Radiology at Memorial Hospital for Cancer and Allied Diseases, as well as an Associate Member within Memorial Sloan-Kettering Cancer Center. He holds a joint appointment in the Molecular Pharmacology and Chemistry Program at the Sloan-Kettering Institute.
Dr. Lewis' research interests are focused on the development of new PET radiopharmaceuticals for the diagnosis and treatment of cancer. His work incorporates 18F, 11C, and nonstandard nuclide radiopharmaceutical development, with an emphasis on cancer detection and therapy. The Lewis Lab research program is a molecular imaging-based program focused on the targetry of nonstandard nuclides as well as the development of small- and biomolecule-based agents and their clinical translation. The Lewis Lab has worked on the development of small molecules targeting hypoxia, as well as radiolabeled peptides and antibodies targeting the overexpression of receptors and antigens on tumors. Currently, specific projects include:
Radiopharmaceuticals for the PET Imaging of Topo-II Expression in Tumors. Topoisomerase-II (Topo-II) is an essential enzyme in the DNA replication process and is the primary cellular target for many of the most widely used and effective anticancer agents. Inhibitors of Topo-II act as cellular poisons and represent a key area of cancer therapeutics. There are, at present, over 100 Topo-II inhibitors in development or on the market. Developing novel imaging methods to systematically explore and quantitate Topo-II-alpha levels in tumors, a previously unexploited target for noninvasive imaging, is potentially paradigm-shifting. Topo-II-alpha targeted imaging agents have the potential to become sensitive probes for diagnosing cancer and monitoring therapy on an individualized basis.
pH (Low) Insertion Peptide Collaboration with the University of Rhode Island and Yale University. The proposed research is based on the discovery of the water-soluble peptide pH (Low) Insertion Peptide (pHLIP), which selectively targets cancer cells by exploiting the intrinsically low extracellular pH of tumors. We have already shown that the pH-dependent insertion of pHLIP within cell membranes allows for the targeting of tumors and the delivery of molecules to cancer cells by exploiting low extracellular pH (<6.5). At the pH of normal healthy tissue, pHLIP weakly interacts with the surface of the cell membrane without insertion into it. We have taken the pHLIP peptide and tagged it with 64Cu, and we have successfully PET-imaged tumors in vivo in mice. This work has demonstrated the proof of concept that we can develop novel PET agents based on the targeting of tumor acidosis.
PET Imaging of Fatty Acid Synthase in Prostate Cancer. The varied response of prostate cancer to therapy indicates that there are large differences in the physiology of tumors in prostate cancer patients. This proposal is aimed at delineating the relationship between 1-11C-acetate PET and the tumor expression of fatty acid synthase (FAS) and determining whether this relationship can be used as a predictive marker for the response of a tumor to conventional therapies.
An Interview With Jason Lewis
"For me, the potential clinical application of my research is incredibly important"
The pursuit of new PET radiopharmaceuticals for the diagnosis and treatment of cancer is the main priority and will require strong collaborations between the lab and fellow scientists. 18F radiopharmaceuticals remain the workhorse of the PET facilities given the availability of the nuclide and the wealth of exceptional 18F-based radiopharmaceuticals. The design and development of 11C agents is also important given that they allow us to perform repeat imaging on a relatively short timescale. However, some agents (e.g., peptides and proteins) require longer-lived radionuclides, and thus we must continue with the high-yield production of nonstandard radionuclides on our in-house cyclotron, including a few others, to produce an arsenal of nuclides that can be available depending on the application. To have on-demand access to the nuclides 64Cu, 86Y, 89Zr, 76Br, 94mTc, and 124I significantly strengthens any PET research program because of their biological importance as well as the fact that they can all be produced in good to high yields on a small cyclotron. This will also involve the development of automated production systems for the separation and isolation of high-purity radionuclides in order to improve productivity while lowering the absorbed doses to production personnel.
