Memorial Sloan Kettering’s cyclotron and GMP production facility
At Memorial Sloan Kettering, researchers have translated numerous new radiopharmaceuticals into the clinic for both imaging and therapy purposes. The Radiochemistry and Molecular Imaging Probe (RMIP) Core Facility serves these investigators by supplying a variety of radiopharmaceuticals , including radiolabeled small molecules, peptides, antibodies, and nanoparticles that can be imaged by methods such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). It also supplies nonradioactive molecular imaging probes for use with non-nuclear detection systems. Our services support both basic research investigations and patient imaging.
The facility intersects many clinical and research areas including cancer biology, medicine, chemistry, physics, radiochemistry, pharmacology, and engineering. As such, it is one of the largest manufacturing units at Memorial Sloan Kettering in terms of the number of clinical and research products it produces.
The RMIP offers the following services:
The Cyclotron Facility
Our cyclotron facility operates two cyclotrons:
- An EBCO (TR19/9) variable beam energy cyclotron on 72nd Street produces 18F, 124I, 86Y, and 89Zr positron-emitting radionuclides for research and clinical applications. These nuclides have a half-life ranging from a few minutes to a few days.
- A GEMS PETtrace-800 cyclotron with QC and labeling equipment, ancillary hotcells/minicells, and GMP production facilities. This instrument was installed in Memorial Hospital in 2013 to enhance MSK’s basic science and clinical translation research programs that rely on PET nuclides. The PETtrace-800 cyclotron is a fully automated machine that is capable of producing 15O, 13N, 11C, and 18F.
Small Molecule Radiochemistry
The Small Molecule Radiochemistry Section incorporates cyclotron-produced positron-emitting radionuclides into precursor molecules to make radiopharmaceuticals used as diagnostic agents in combination with PET imaging. These radiopharmaceuticals are designed to detect primary and metastatic tumors and provide better delineation of tumor boundaries. The powerful combination of radiolabeled tracers and PET imaging can provide information on functional changes well ahead of the detection of structural changes by imaging tools such as x-ray or CT. Radiolabeled pharmaceuticals, which decay with time, are synthesized individually on the premises for both research and clinical studies.
The Antibody Labeling Section is responsible for the radiolabeling of peptides and monoclonal antibodies for cancer diagnostic (radioimmunoimaging) and therapeutic (radioimmunotherapy) purposes. Applied as a targeted therapy, radioimmunotherapy utilizes these radiolabeled monoclonal antibodies to selectively target tumor cells, delivering a potentially lethal dose of radiation to the cancer cells without harming normal cells. Radionuclides are primarily produced on our in-house cyclotron or are obtained from commercially available sources for these purposes.
Currently Available Agents
The RMIP Core Facility has been successful in synthesizing and supplying existing radiopharmaceuticals, as well as in developing novel radiopharmaceuticals and translating these agents into the clinic.
See Table 1 for a current list of agents we provide.
Future Technological Developments
Our molecular imaging experts continue to develop new, highly selective tracers that will play a huge role in the diagnosis and treatment of cancer — especially when used in combination with novel cancer drugs that are being developed worldwide.
Fluorine-18 (18F) radiopharmaceuticals will remain the workhorse of PET facilities because of the availability of the nuclide and the wealth of exceptional 18F-based radiopharmaceuticals. However, the design and development of carbon-11(11C) agents are also important because carbon is present in almost every biological molecule and in more than 98 percent of pharmaceuticals. Agents based on 11C can be effectively used for several different applications, including cancer diagnosis. With the construction of a new cyclotron facility, we will be able to synthesize carbon-11–based tracers for clinical use. In addition, we will have a toolbox of targeting radiolabeled drugs that will allow us to augment existing research programs for the development of personalized cancer medicine. Because PET drugs are likely to play a vital role in the monitoring of conventional and new therapies, there is an increasing demand for highly specific imaging surrogates or chemically analogous agents.
The Observer Program
The RMIP Core Facility offers a training program for research staff at other institutions to learn about the following:
- How to prepare chemistry, manufacturing, and control (CMC) documentation and investigational new drug (IND) applications for new radiopharmaceuticals
- Manufacturing radiopharmaceuticals in compliance with cGMP regulatory requirements
- Working in controlled GMP environments (cleanrooms) and utilizing aseptic techniques
- Quality assurance for radiopharmaceuticals prepared for both clinical use and clinical research use
- Quality control (release testing) for radiopharmaceuticals prepared for human use
- Developing and validating new analytical methods
- Developing, implementing, and managing standard operating procedures (SOPs)
- Dispensing radiopharmaceuticals
- Producing novel radionuclides
- Conjugating and radiolabeling monoclonal antibodies
This program can be tailored toward individual needs. For more information and costs, please contact RMIP Core Director Jason S. Lewis.
Our clinical research radiopharmaceuticals (see Table 1) are manufactured in compliance with the FDA’s federal regulation 21CFR212, Current Good Manufacturing Practice for Positron Emission Tomography Drugs (2019); FDA cGMP guidances for PET drugs; and United States Pharmacopeia Chapter 823, Radiopharmaceuticals for Positron Emission Tomography — Compounding. Injectable radiopharmaceutical sterility is assured through compliance with United States Pharmacopeia Chapter 797, Pharmaceutical Compounding — Sterile Preparations, and by using state-of-the-art controlled-environment facilities compliant with International Organization for Standardization standards, titled ISO-14644 Cleanrooms and Associated Controlled Environments. Once the new facilities are complete, the RMIP Core Facility will manufacture radiopharmaceuticals such as 18F-fluordeoxyglucose, 18F-sodium fluoride, and 13N-ammonia, pursuant to FDA-approved aNDA applications. The facility will be registered with the FDA as an approved PET radiopharmaceutical manufacturer.