Radiochemistry & Molecular Imaging Probes -- Core Facility

Jason Lewis (Core Facility Head)

Molecular imaging (MI) is one of the most rapidly advancing specialties in medicine. The MI scientists at Memorial Sloan Kettering have established a vibrant and state-of-the-art laboratory-based translational research program, in addition to a world-class clinical research and care operation. In support of this program is the Radiochemistry and Molecular Imaging Probe (RMIP) Core Facility. Cyclotron Memorial Sloan Kettering’s cyclotron and GMP production facility The RMIP Core Facility portfolio is situated at the intersection of Memorial Sloan Kettering research and clinical MI initiatives — including cancer biology, medicine, chemistry, physics, radiochemistry, pharmacology and engineering and, as a direct consequence, has evolved as one of the largest manufacturing units at Memorial Sloan Kettering in terms of the number of clinical and research products produced.

The RMIP Core Facility provides basic researchers and clinical investigators institution-wide with radionuclides, radiolabeled pharmaceuticals, radiolabeled antibodies, and molecular imaging probes. These probes are administered to the subjects and imaged using specialized cameras such as PET or SPECT for disease detection.

The facility consists of three major elements working closely together to provide 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.

The Small Molecule Radiochemistry Section

The Small Molecule Radiochemistry Section incorporates cyclotron-produced positron-emitting radionuclides into precursor molecules to make radiopharmaceuticals. In combination with PET imaging, these radiopharmaceuticals are used as diagnostic agents, 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 structural changes that other imaging tools such as X-ray or CT cannot identify. Radiolabeled pharmaceuticals, which decay in a short period of time, are synthesized on demand on the premises for both research and clinical studies.

The Antibody Labeling Section

This Antibody Labeling Section is responsible for the radiolabeling of peptides and antibodies as requested by preclinical and clinical investigators for both cancer diagnostic (radioimmunoimaging) and therapeutic (radioimmunotherapy) purposes. Applied as a targeted therapy, radioimmunotherapy utilizes these radiolabeled monoclonal antibodies to selectively target tumor cells and deliver a potentially lethal dose of radiation to the cancer cells without harming normal cells. Radionuclides are primarily produced on the in-house cyclotron or are obtained from commercially available sources for these purposes.

Currently Available Agents: The RMIP Core Facility has been extremely successful both in synthesis and supply of existing radiopharmaceuticals and also in translating and supplying novel radiopharmaceuticals developed in-house at MSKCC for several clinical trials. This is in addition to supporting an extensive basic science program with a consistent supply of nuclides, research drugs, and chemistry/radiolabeling expertise. This has been achieved by creating a program based on cutting-edge research in tandem with strong collaborations between nuclear medicine physicians, imaging scientists, molecular biologists, chemists, pharmacologists, physicists, radiochemists, immunologists, and medical, surgical, and radiation oncologists. View the current list of agents available for the clinic.

Future Technological Developments: Memorial Sloan Kettering has an active and vibrant radiochemistry and nuclear medicine program. We have translated numerous novel radiopharmaceuticals to the clinic for both imaging and therapy purposes, and continue to develop new, highly selective tracers that will play a huge role in the diagnosis and treatment of cancer, especially with regard to investigational therapeutic cancer drugs that are being studied worldwide. Fluorine-18 (18F) radiopharmaceuticals will remain the workhorse of PET facilities given 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 more than 98 percent of pharmaceuticals, and therefore can be effectively used for several different applications including cancer diagnosis. With construction of our new cyclotron (connected via pneumatic tube to seven basic science and clinical sites center-wide) under way, we will be able to synthesize 11C-based tracers and supply them to the clinic.

Regulatory Compliance: Our clinical research and clinical 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. The new facility will be registered with the FDA as an approved PET radiopharmaceutical manufacturer.

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.