Theranostics and Particle Therapy

A key focus of the initiative is translational research, beginning in the laboratory and translating to clinical work in the form of new therapies or diagnostic techniques. Investigators are assessing how particle beam radiation may be effective in treating cancers that are resistant to conventional radiation therapy; how diagnostic and treatment steps can be combined into a single step — a process known as theranostics; and how radiation treatment plans can be personalized for each patient.“We have a unique combination of unparalleled strengths here at University of Wisconsin–Madison,” says Zachary Morris, MD, PhD (PG ’16), co-director of the initiative and chair of the Department of Human Oncology at the UW School of Medicine and Public Health (SMPH). “This makes our campus the perfect setting for this initiative.”

Particle Therapy: Precision for Patients

For some patients, traditional radiation therapy is not ideal. For example, depending on the location of the tumor, traditional radiation methods could expose neighboring healthy tissue to radiation doses that would exceed safe limits. Also, therapy for pediatric cancers often includes a goal of limiting the patient’s radiation exposure. In such instances, particle beam radiation may be a preferred treatment.

Some researchers and clinicians with the Initiative for Theranostics and Particle Therapy focus on particle beam radiation used in proton therapy, in which radiation travels to a specified depth in the tissue and stops, reducing the radiation exposure to healthy tissues and sparing treatment-related toxicities.

Theranostics: Diagnosis Combined with Therapy

Targeting tumors typically requires using medical imaging to locate the precise position of a tumor during treatment. If there are many tumors to target throughout the body, particularly small and microscopic tumors, this can be impossible.

To address this challenge, researchers with the initiative focus on radiopharmaceutical therapy, also known as targeted radionuclide therapy (TRT). This type of therapy involves injecting an agent that selectively delivers radiation to tumors no matter their size or location. These agents have been shown to prolong survival for many patients, including those with certain forms of thyroid, prostate and neuroendocrine cancers, as well as pediatric neuroblastoma.

“Investigators at SMPH and UW Health are pioneering the development of novel TRT agents and testing these in combination with other cancer treatments like immunotherapies, with the goal of curing cancer in patients previously believed to have incurable disease,” Morris explains.

Depending on the form of radioactivity attached to the radiopharmaceutical, the same TRT agent can be used not only for cancer therapy, but also as a new way to detect and image cancers using advanced technologies such as positron emission tomography (PET). The combination of PET molecular imaging and TRT provides a powerful tool for diagnosis and therapy. These agents are called “theranostics” due to this dual therapy and diagnostic role, according to John Floberg, MD ’14, PhD ’12, assistant professor, SMPH Department of Human Oncology, and radiation oncologist, UW Health.

“Researchers with the initiative will be doing critically important work to advance the translation of theranostics and particle therapy into curative treatments for patients with metastatic cancers,” Floberg notes.

Describing the Theranostics Disease-Oriented Team (DOT) that has been created in the UW Carbone Cancer Center, Steve Cho, MD — chief, Section of Nuclear Medicine and Molecular Imaging, SMPH Department of Radiology — says, “We have been developing the infrastructure and workflow for a multidisciplinary group that includes faculty and staff from SMPH, UW Health and the cancer center. This has positioned us well to meet the clinical standard-of-care needs and emerging clinical research opportunities in theranostics.”

A co-director of the Theranostics DOT and professor of radiology, Cho continues, “Our team is uniquely positioned to deliver the highest level of theranostics clinical care and bring the most promising theranostics treatments to our patients.”

Dosimetry: Personalized Doses for Treatments

Theranostic imaging allows doctors to measure precisely how impactful a TRT is for each patient’s cancer cells. By leveraging that capability, SMPH researchers also have developed technologies that allow doctors to use theranostic images to personalize the prescription of a TRT so it is maximally effective and safe for each patient. The process of identifying patient-specific amounts of a radiopharmaceutical therapy drug is called dosimetry, according to Bryan Bednarz, PhD, professor, SMPH Department of Medical Physics.

Dosimetry enables doctors to tailor treatments with greater precision than relying on standard dosage guidelines alone, allowing them to develop personalized dosage plans that maximize effectiveness while minimizing potential harm in patients, he says.

Bednarz adds, “This combination of advancements is a critical component of the future for cancer diagnosis and therapy.”

Synergy Among Areas of Expertise

“This initiative is uniquely cooperative,” says Morris. “It provides a central mechanism for individuals involved in these fields to engage with one another and put ideas together for collective advancement. This area is inherently multidisciplinary. If we stay in our silos, we only get so far, but when we work together, we can see the confluence of opportunities.”

Initiative researchers are working to develop novel cancer-targeted molecular imaging and radiotherapy TRT agents; produce more effective theranostic imaging and particle therapy; advance dosimetry methods; and translate discoveries into clinical practice.

Faculty members associated with the initiative also plan to establish premier graduate and fellowship training programs for researchers and practitioners in theranostics, particle therapy, dosimetry, and nuclear and radiochemistry, according to Jamey Weichert, PhD, professor, SMPH Department of Radiology, and co-director of the initiative.

“We are creating a destination theranostics and particle therapy clinical center at UW Carbone Cancer Center with this work,” says Weichert.

The initiative has membership criteria for researchers and clinicians at SMPH and UW Health who work in these areas and wish to become involved. The unit is governed by an executive board of six UW–Madison faculty members who engage in research, clinical care, and education related to theranostics and particle therapy.

This work is possible thanks to major federal funding provided to UW–Madison, including the first National Institutes of Health-supported program project grant for theranostics, explains Anjon “Jon” Audhya, PhD, senior associate dean for basic research, biotechnology, and graduate studies at SMPH.

“Over the last several years, our outstanding investigators have competed successfully for nationally recognized awards related to theranostics,” Audhya says.

The funding includes a recent $8 million grant to construct a new, national, theranostic cyclotron resource center that will drive fundamental and translational medical science. It also includes $20 million in grants from the National Cancer Institute, and a $1.5 million seed investment from the Wisconsin Alumni Research Foundation, according to Audhya.

He adds, “This support is critical because, ultimately, our goal is to be the preeminent site for preclinical and clinical theranostics research around the globe.”

Coming Attraction: Proton Beam Therapy

by Kris Whitman

Within the University of Wisconsin School of Medicine and Public Health’s (SMPH) Initiative for Theranostics and Particle Therapy, some faculty and staff members are focusing on particle beam radiation used in — for example — proton therapy. This type of radiation travels to a specified depth in the tissue and stops, thus reducing radiation exposure to healthy tissues and sparing treatment-related toxicities.

As research and training related to proton beam therapy continue in the Wisconsin Institutes for Medical Research, UW Health and the UW Carbone Cancer Center are advancing the first academic program in the world with upright proton therapy. Proton beam is among the most precise forms of radiation treatment that can target complex tumors that are close to vital organs. The ability to limit the delivery of radiation outside the tissues being treated is a major benefit when treating children who are still growing.

Traditional proton therapy is delivered to a patient lying on their back or stomach, while upright proton therapy will be delivered to patients who are sitting, enhancing comfort while taking advantage of more natural organ positioning. The upright technique developed by Leo Cancer Care allows treatment for patients with underlying health conditions — such as certain heart or lung conditions — that can make it difficult to lie flat for the duration of therapy. Upright patients also can interact more easily with health care professionals. For children, this may reduce the need for sedation during treatment.

For more than a decade, Paul Harari, MD, has focused attention on bringing proton beam therapy to UW Health. Following a rigorous evaluation of worldwide proton beam manufacturers, UW Health selected Hitachi in Tokyo to make this a reality. Harari explains that the new facility in Madison, being constructed at UW Health’s Eastpark Medical Center, “could be a paradigm changer because of the improved humanity for patients to interact with providers in the upright position and the more natural organ position that may offer advantages for normal tissue sparing. In addition, most patients are simply more comfortable being upright.”

A professor in the Department of Human Oncology, Harari describes the unique requirements and remarkable efforts of the planning and construction teams building the proton facility.

“The walls of proton vaults are seven to eight feet thick, with highly specialized techniques for pouring the concrete to shield and contain the radiation,” Harari says, adding that more than 13,000 tons of concrete and over 400 tons of rebar were used in the overall construction of the proton facility by UW Health.

Noting that the proton beam equipment will be transported across the Atlantic Ocean and to Madison in 2025, Harari says, “The best part is that inside these specialized proton treatment vaults, the lives of children and adults with cancer will be positively impacted for decades. This is what our multidisciplinary teams of cancer professionals are trained to do.”