Molecular imaging (MI) has been used in medicine for more than 30 years to visualize, characterize, and quantify biological processes taking place in the body. Using positron emission tomography (PET) or single-photon emission computed tomography (SPECT) scanners, clinicians follow the path of radiopharmaceuticals — compounds designed to latch on to specific receptors inside the body, to offer functional information about a disease. These radiopharmaceuticals are typically paired with a radioactive isotope such as fluorine-(18F), which behaves like a radio beacon and allows doctors to see what it binds to inside the body.
In contrast to structural imaging, MI procedures enable clinicians and researchers to better understand the function and status of the disease, providing an opportunity to intervene with earlier and tailored treatment strategies. In oncology, MI can visualize and characterize tumors, enabling accurate diagnoses and monitoring to help determine appropriate treatment pathways.
New technologies and approaches are being developed with the aim of delivering to clinicians even more detailed pictures of different types of cancer cells in order to select the best patients’ candidates for specific therapies, monitor the progress of treatment, and kill cancer cells without affecting the healthy tissue.
GE HealthCare is part of that future. In October 2023, it announced collaborations with SOFIE Biosciences and Nucleus RadioPharma that will play an even larger role in developing and marketing the next generation of molecular imaging pharmaceuticals.
“For many years there was some innovation bubbling around in this space,” says Julia Casey, general manager of molecular imaging at GE HealthCare’s Pharmaceutical Diagnostics business. “In the last five years or so, that has really accelerated in terms of products getting closer to market — and their success in supporting patient outcomes — and people seeing the value of molecular imaging.”
Cancer associated fibroblasts (CAFs) and the tumor microenvironment
A promising new approach
PET scanners typically rely on radiopharmaceuticals that bind directly to a variety of cells involved in disease. SOFIE has taken this approach through clinical development of two diagnostic agents called [68Ga]FAPI-46 and [18F]FAPI-74. These products belong to the family of compounds called fibroblast activation protein inhibitors (FAPI) and were licensed from Heidelberg University. Using the isotopes gallium-68 and fluorine-18, respectively, the agents target the fibroblast activation protein (FAP) that clusters around cancerous tumors. Both tracers are currently in phase 2 clinical trials in the U.S.
“FAP is typically not expressed on the tumor cell itself, except for a few rare cases, such as sarcomas, but instead it is expressed in the environment, called the stroma, that allows the tumor to survive and thrive,” says Sherly Mosessian, Ph.D, SOFIE’s chief scientific officer. “Its value is in helping us understand where the cancer is, if the cancer has metastasized, what the treatment may be, and which patients may respond best to the therapy.” Unlike other diagnostic agents, [68Ga]FAPI-46 and [18F]FAPI-74 are able to target a variety of cancers, including ovarian, pancreatic, lung, breast, gastric, and colorectal.
In October 2023, GE HealthCare (GEHC) took on global rights for [68Ga]FAPI-46 and non-U.S. rights for [18F]FAPI-74 for development, manufacturing, and commercialization. SOFIE will maintain [18F]FAPI-74 in the U.S., in addition to SOFIE and GEHC working collaboratively through their joint steering committee to shape the strategic direction for the future of FAPI. This promotes a global reach to these very promising tracers. In addition to the prospective phase 2 studies with these tracers in the U.S., SOFIE has established a growing FAPI Global Outreach Program, supporting academics in 142 unique institutions in 39 countries, who are working on 265 studies that will help unlock of the potential of these products and subsequent clinical approvals. Working with GE HealthCare will allow for a more robust global effort in management of clinical approvals toward the use of FAPIs in detecting a variety of diseases in addition to cancer, such as inflammation, fibrosis, and arthritis, and in serving as companion diagnostics to various therapeutics.
Theranostics: A one-two punch
Theranostics (a combination of “diagnostics” and “therapy”) uses radiopharmaceuticals to target cancer cells the same way some imaging technology does, but in this case the particles deliver a much higher dose of radiation. The goal with theranostics is to kill the cancer cells without harming any of the healthy tissue. It is, Casey says, one of the main reasons the molecular imaging field has been growing so rapidly in recent years.
Since 2022, Nucleus RadioPharma has been developing theranostic drugs that target prostate cancer. GE HealthCare, along with a number of other organizations, has agreed to provide series A funding to help Nucleus accelerate its various initiatives, including drug development and building an integrated radiopharmaceutical contract development and manufacturing organization (CDMO) and supply chain facility in Rochester, Minnesota, home of the Mayo Clinic, which uses more theranostics on its patients than any other medical center in the U.S.
More than $5 billion has been invested in theranostics companies in the past five years, says Charles Conroy, CEO of Nucleus, and 75 new companies have launched. Nucleus has been working with many of them.
“The role of the CDMO is really twofold,” says Conroy. “One part is to make sure that all these companies have access to the expertise so they can get through the clinical and regulatory process. And then there’s the manufacturing aspect, which is making sure we can actually get these things to market, especially with drugs like these that are so hard to develop and environmentally sensitive.”
“It’s one thing to be able to manufacture them and take them down the hallway,” Conroy continues. “It’s another thing to manufacture them to make sure you can treat patients all the way across the world.”
One of the difficulties with radiopharmaceuticals is that isotopes have short half-lives, many just an hour or two, and distributors have to plan very precisely to get them to hospitals while they are still usable. So far, there is no established supply chain for radiotherapeutics between lab and treatment center, but Nucleus aims to build one. GE HealthCare’s many facilities worldwide will also be a help.
“Our strategy for molecular imaging in oncology is simply to enable precision care,” Casey says. “We’re working on specific biomarker targets to support clinicians in getting a better idea of the biology of their patients, helping them make more personalized treatment decisions. There are significant opportunities to tackle unmet needs in oncology through areas like FAP, theranostics, and immuno-oncology. We are working to help shape the future of molecular imaging by collaborating to deliver on their potential.”
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