​Theranostics ─ A Bold New Tool for Fighting Cancer

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​Theranostics ─ A Bold New Tool for Fighting Cancer

As mentioned in our opening memo, theranostics is a breakthrough technology you’ll be hearing a lot about in the future. Loma Linda University Health (LLUH) is collaborating with BAMF Health on this venture. Both institutions are in the process of establishing theranositc centers at their respective headquarters. Both LLUH and BAMF are already collaborating on developing new theranostic agents.

The following article was written for the BOB Tales by Mark Reeves, MD, PhD, Cancer Center Director at LLUH. Dr. Reeves is in the process of establishing a Comprehensive Cancer Center at Loma Linda, designated by the National Cancer Institute. One of their initiatives is to pursue and develop this new technology.

The article is somewhat technical for many of our members, but the importance and significance of this new technology is clearly evident.

We encourage you to carefully read this important article and consider the implications of using this breakthrough technology for treating advanced, metastatic prostate cancer as well as a whole range of other cancers previously untreatable with today’s technologies. This new technology is totally consistent with the proton therapy concept of destroying disease while minimizing damage to surrounding healthy tissue. And you’ll see in this article how theranostics and proton therapy can, and will be, synergistic technologies.

This is truly exciting news.

Theranostics

By Mark Reeves, MD, PhD, Cancer Center Director, LLUH

Theranostics is an emerging field that combines molecular therapies (therapy) and paired molecular targeted imaging (diagnostics). In oncology, a molecule that binds to a tumor is first used to image the cancer, and then that same molecule is used to destroy the cancer. This approach is being used to transform many fields in medicine, especially neurosciences and oncology. It has the promise of moving oncology from “trial-and-error medicine” to “precision medicine.”

An Example

Theranostics is already transforming the diagnosis and treatment of rare, difficult-to-treat neuroendocrine tumors. We have known for a long time that they universally bind to a molecule called “somatostatin.” Based on this, a version of somatostatin called “DOTATATE” is connected to diagnostic radioisotopes (68Ga) that can be detected using positron emission tomography (PET/CT). Thus, 68Ga-DOTATATE is injected into a patient with a neuroendocrine tumor, and a very specific PET/CT is obtained that finds both the primary tumor and sites of spread that can’t be seen on typical scans.

Then, after all the sites of tumor have been identified, the same molecule (DOTATATE) is hooked to a therapeutic isotope (177Lu) that creates lethal radiation in the local area where the DOTATATE binds. 177Lu-DOTATATE is infused into the patient; it seeks out the sites of cancer; and the 177Lu destroys it with localized radiation. It can be thought of as a system that seeks (68Ga-DOTATATE) and precisely destroys (177Lu-DOTATATE) the cancer, leaving other tissue alone.

Scratching the Surface

This is good, but neuroendocrine tumors are rare. Can theranostics be used for more common cancers such as prostate cancer? Yes.

The most well-known example of this is prostate-specific membrane antigen (PSMA). PSMA is a glycoprotein that is highly expressed in prostate cancers. More important, it is more highly expressed in high-risk and metastatic prostate cancer.

PSMA is being developed as a theranostic agent to detect and treat prostate cancer. The data supporting 68Ga-PSMA-11 (a ligand that binds to PSMA) PET/CT scanning for prostate cancer are compelling. PSMA PET/CT is far more sensitive than bone scanning or fluciclovine PET/CT, and in one study changed treatment decisions in 62 percent of patients with biochemically recurrent prostate cancer. PSMA is also being developed as a paired therapy (eg: 177Lu-PSMA-11) for prostate cancer. Early data are showing significant responses to PSMA therapy even in heavily pre-treated patients with widely metastatic disease. While not available outside of a clinical trial in the U.S., it is available in Europe.

Development of New Compounds

Because not every prostate cancer binds PSMA, the development of new compounds that bind to prostate and other cancers is critical. In the new Molecular Imaging and Therapeutics Research Program (MITRP) in the LLU Cancer Center (directed by Frankis Almaguel, MD, PhD), we have used boron chemistry to synthesize and develop molecules that bind to a number of prostate and other cancer biomarkers (eg: enolase, FAPI, MetAP2, etc).  These molecules are then developed into theranostic pairs to image and treat cancer.

A New Theranostics Center

To leverage this theranostic approach to precision cancer therapy, Loma Linda University Cancer Center is developing a Theranostics Center as part of the MITRP in collaboration with BAMF Health. “We are excited to partner with LLUCC to bring this futuristic but real technology to the patients in a high speed manner. This partnership will make a significant impact to the future of cancer care with a strong research capability in proton therapy, health disparity, and other cancer related fields within LLU community,” said Dr. Anthony Chang, founder and CEO of BAMF Health. The Theranostics Center is being developed in three phases: ​

Phase 1, which went live March 1, is a consultation clinic that makes theranostic consultations available to patients under the direction of Dr. Almaguel. 
 
Phase 2, which we anticipate being active in 2022, will create a dedicated theranostics clinic, which will contain both dedicated molecular imaging facilities and a precision therapy and infusion clinic. It will allow us to provide both standard and experimental theranostic imaging and treatment. 
 
Phase 3, which is planned to be active in 2-3 years, will leverage our existing cyclotron capabilities to create a full theranostics program. This will provide expanded molecular imaging and precision therapy clinics, full synthetic radiopharmacy capabilities, synthesis and translation of novel molecules into early-phase clinical theranostics trials, and the utilization of artificial intelligence to provide more efficient and precise therapies. Particularly exciting about this program is the full translational ability to conceptualize and synthesize compounds in the chemistry lab, develop them in sophisticated animal models, and bring them to early phase human use in a short period. 

Theranostics and Proton Therapy

Adding further to the excitement about theranostics is the obvious connection to proton therapy and other particle therapies such as boron neutron-capture therapy (BNCT). We have already started integrating PSMA theranostics into proton therapy planning, and will combine these modalities in future clinical trials. Imagine for a moment, patients newly diagnosed with prostate cancer receiving theranostic molecular imaging with PSMA or other newer compounds and using these results to decide on the best approach to treatment. For instance, if the theranostic scan showed disease only in the prostate, then proton therapy might be chosen as the best treatment approach. Better yet, if the scan showed that only a specific part of the prostate had disease, then only that part of the prostate might be treated with proton therapy, potentially further lowering side effects. If the scan showed minimal distant metastatic disease and significant disease in the prostate, then the best approach might be up-front therapy with the theranostic agent, which would seek out and destroy the metastatic sites of disease. Proton radiation might then be used to treat any residual disease in the prostate.

All these approaches obviously need to be developed and tested in clinical trials, and there are many other potential synergies between theranostics and particle therapy. While this will require time and investment of resources, we believe that the co-location of theranostics and proton centers at LLUH make it the obvious place to develop and deliver these precision cancer treatment approaches.

► BOB Comment: We reached out to Dr. Reeves and asked for more details about the timing of implementation of the theranostics program at Loma Linda that may benefit BOB members with recurrent cancer. He said, “We hope to have our theranostics center up and running and able to provide this therapy in 2022. Patients can be seen before then, however, to determine if they’re candidates for PSMA therapy.”

https://protonbob.com/2021-05-protonbobtales

Science Resources
https://pubmed.ncbi.nlm.nih.gov/23286214/