Frida Westerbergh: Treatment optimizations for metastatic Cancer: SPECT imaging with a new generation of radiopharmaceuticals
Radionuclide therapy is at a crossroads. Currently, all patients receive the same treatment, although their individual tolerance may vary significantly. With SPECT imaging, the patient’s personal response can be mapped out and therapy can be tailored for greater impact. Making this possible requires imaging methods that ensure high image quality — the scope of this thesis.
FRIDA WESTERBERGH
Dissertation defense: 5 june 2025 (click for details)
Doctoral thesis: I
Research area: Medical Radiation 91̽s
Sahlgrenska Academy, The Institute of Clinical 91̽s
The use of radioactive, tumor-targeting drugs — known as radionuclide therapy — has proven to be an effective strategy for treating metastatic cancer. However, complete remission is rarely achieved. One possible reason is that current radionuclides do not have optimal radiation properties. Another is the lack of personalized treatment, meaning some patients may be undertreated.
With a SPECT camera* and radioactive drug, we can generate 3D images showing how the drug accumulates throughout the body. This allows us to calculate the radiation dose delivered to both tumors and healthy organs (a process known as dosimetry). Imaging therefore becomes a key tool in optimizing treatment.
“In my thesis, I explore a new radionuclide, terbium-161 (¹⁶¹Tb), which shows promising potential for radionuclide therapy. However, to use it reliably for dose calculations, we need robust imaging protocols — and those don’t currently exist. That’s the knowledge gap I aim to help close,” says Frida Westerbergh, licensed medical physicist, member of the PhONSA research group (Medical Physics, Oncology and Nuclear Medicine Research Group at Sahlgrenska Academy), and a doctoral student at the Institute of Clinical 91̽s.
Terbium-161 (¹⁶¹Tb) is a new and promising therapeutic radionuclide. Its unique radiation characteristics make it suitable for treating both large and small tumors, which could lead to more effective therapy for metastatic cancer, especially in cases involving micro metastases.
There are some technical pitfalls to be aware of
The dissertation shows that accurate radiation dose calculations with ¹⁶¹Tb are possible, but there are technical challenges to be mindful of. For instance, current imaging systems have limitations in how much radioactivity they can handle. This becomes especially relevant for ¹⁶¹Tb, due to its slightly unusual radiation emission pattern.
“To carry out SPECT-based dosimetry with sufficient accuracy, imaging protocols must be tailored to the specific radionuclide in use. The image processing also needs to account for several radionuclide-specific factors that can degrade image quality.”
The dissertation examines how imaging with ¹⁶¹Tb should be performed to achieve high-quality results. The methods developed are currently being used in two clinical studies at the University Hospital in Basel, where two ¹⁶¹Tb-based drugs are being tested in humans for the very first time.
“These trials involve patients with neuroendocrine tumors and prostate cancer. In both studies, SPECT-based dosimetry allowed us to observe higher radiation doses to tumors, compared to existing treatments — without any added harm to healthy
Figure 5.6 from the dissertation: SPECT images taken at different time points after infusion in a patient treated with the new drug [¹⁶¹Tb] Tb-DOTA-LM3 for neuroendocrine tumors at the University Hospital in Basel, Switzerland. The dissertation describes how the imaging protocol was designed and how radiation dose calculations were carried out. Compared to the clinically established drug [¹⁷⁷Lu] Lu-DOTATOC, the new approach resulted in significantly higher tumor doses without added harm to healthy organs
This thesis sheds light on both the challenges and opportunities of image-based ¹⁶¹Tb dosimetry. In doing so, it contributes to the evolution of radionuclide therapy into a truly personalized treatment for patients with metastatic cancer.
Being part of valuable research – both rewarding and demanding
– “Working hands-on with radioactivity is understandably a bit stressful — you must get everything done before it decays. One of the biggest challenges has also been taking on a leading role in two international clinical studies. But despite, or maybe because of that, my PhD journey has been incredibly rewarding. I'm very grateful for all I've learned, and proud to have contributed to research that could make a real difference for people with advanced cancer.”cancersjukdom.
Text: Susanne Lj Westergren
* Radionuclide: An unstable (i.e., radioactive) substance that emits radiation as it transitions to a more stable state.
* Radionuclide Therapy: A type of internal radiation therapy in which radionuclides are combined with tumor-seeking molecules.
* SPECT Camera: A nuclear medicine imaging technique that, when paired with a radioactive drug, allows doctors to visualize how the body functions. It’s like a reverse X-ray — instead of producing radiation with an X-ray tube, the patient becomes the source, and rotating detectors capture the radiation from the outside.