Enhancing Prostate Cancer Radiotherapy Precision With Gallium 68 PSMA-11

Chunhui Han, PhD

Biology-guided radiotherapy (BgRT) is a groundbreaking technique in radiation oncology that offers an innovative approach that leverages radiotracers to precisely target tumor sites.^1,2 With this approach, patients are injected with radiotracers that bind to tumors that can then be detected by imaging systems like PET scanners. These signals guide the radiotherapy machine to accurately deliver radiation to the tumors.

Central to this innovation is Gallium 68 (Ga 68) PSMA-11, a radiotracer that was approved by the FDA in 2020. It works for imaging metastatic prostate cancer and targets the prostate-specific membrane antigen (PSMA), which is overexpressed in certain prostate cancers. This allows for the detection of metastatic cancer cells throughout the body using PET scans.

Although promising for BgRT treatments, Ga 68 PSMA-11 is not yet clinically approved for treating metastatic prostate cancer, and substantial preclinical research is required.

In an interview with Targeted Oncology^TM, Chunhui Han, PhD, medical physicist in the Department of Radiation Oncology at City of Hope National Medical Center, discussed his presentation from the 2024 American Society of Therapeutic Radiology and Oncology (ASTRO) Annual Meeting on the use of Ga 68 PSMA-11 for the imaging of metastatic sites in patients with prostate cancer.

Targeted Oncology: Could you explain what biology-guided radiotherapy is and how it differs from traditional radiotherapy techniques?

Conceptual image for viral etiology of prostate cancer: © Dr_Microbe - stock.adobe.com

Han: BgRT is an emerging modality in radiation oncology. In essence, BgRT uses signals from radiotracers to accurately deliver radiation to the intended target. In a BgRT workflow, the patient is injected with certain radiotracers that will preferentially bind with tumor sites throughout the body. Those radiotracers will light up under special cameras, for example, under positron emission tomography scanners. Those signals will tell the machine the location of the tumor, and this will help the radiotherapy machine to deliver radiation where it is intended.

What is Ga 68 PSMA-11 and how does it function?

Ga 68 PSMA-11 is a radiotracer that was approved by the FDA in 2020 to image metastatic sites for [patients with] prostate cancer. It is the first PSMA imaging agent approved for PET scan or PET imaging. PSMA is a molecule, a protein, that can be found in prostate cells, but there is an overexpression of the PSMA for certain prostate cancer types. When they metastasize, you will find prostate cancer cells in other parts of the body, and when we use the PSMA-11 agent, those metastatic sites will also light up under PET scans. So that means you can use Ga68 PSMA-11 as a radiotracer to locate metastatic sites for [patients with] prostate cancer, and that can also be used for BgRT treatments.

How feasible do you believe the integration of Ga 68 PSMA-11 in BgRT for patients with prostate cancer with bony metastases is?

Currently it is not clinically approved for treatment of patients [with] metastatic prostate cancer. There is a lot of preclinical work to be done before Ga 68 PSMA-11 can be used clinically.

At City of Hope, we use the RefleXion X1 as a radiotherapy machine to do BgRT treatments.2 We currently use [fludeoxyglucose (FDG)]-labeled radiotracers to deliver BgRT. Ga 68 PSMA-11 has different physical properties compared with [fluorine F 18 piflufolastat ([18F]-DCFPyL)] FDG. So, for it to be used clinically, there has to be some research to be done.

What are the primary challenges you foresee in implementing this technology in clinical practice?

As I mentioned, there is a physical property difference between Ga 68 PSMA-11 and 18F. For example, Ga 68 decays faster than ¹⁸F. So, that means that the PET signal may gradually become weaker in treatments. That is one challenge for the implementation of Ga 68 in metastatic prostate cancer treatments. Ga 68 preferentially binds with prostate cancer cells that have an overexpression of PSMA. So, that is what makes it ideal to detect and treat metastatic prostate cancer, but there needs to be some preclinical studies to be done before it can be used clinically.

Does the use of Ga 68 PSMA-11 radiotracer improve the targeting and treatment of bony metastases in prostate cancer?

Yes, the use of Ga 68 could potentially facilitate treatment of bony metastatic status in prostate cancer. This study clearly demonstrated the feasibility of using Ga 68 PSMA-11 BgRT for bony metastasis. So, bony metastasis will light up and send a strong signal under the PET scan, and the RefleXion X1 machine uses a PET imaging system to detect signals from bony metastases when Ga 68 is injected, making it a potential candidate for BgRT.

Are there any known or potential adverse effects associated with Ga 68 PSMA-11 that oncologists should be aware of?

Ga 68 PSMA-11 is the first PSMA radiotracer approved by the FDA for PET imaging of [patients with] prostate cancer. There were no severe complications found in prior studies. However, there were some common complications associated with injection with Ga 68 PSMA-11, including nausea, diarrhea, and more as relatively minor complications.

What advancements have been made to support the use of Gallium-68 PSMA-11 in BgRT?

There is active research in the use of Ga 68 PSMA-11 for BgRT. The industry is actively evaluating the feasibility of Ga 68 PSMA-11 in BgRT treatments, and there is also active research at different centers, including City of Hope, on the availability of using Ga 68 PSMA-11 for prostate cancer bony metastasis.

How do you see the future of radiotherapy evolving with the use of biologically guided techniques like BgRT with Ga 68 PSMA-11?

BgRT is an emerging modality, and there is active research on the use and variety of novel radiotracers to facilitate BgRT treatments. In the future, we may see more radiotracers put in clinical use for radiotherapy treatment, and there is also active progress being made in the area where different radiopharmaceutical agents are used for both imaging and for treatment of a variety of cancer types. In terms of BgRT, we will see more and more radiotracers being evaluated with and potentially being implemented clinically for different cancer types.

REFERENCES:

1. Shirvani SM, Huntzinger CJ, Melcher T, et al. Biology-guided radiotherapy: redefining the role of radiotherapy in metastatic cancer. Br J Radiol. 2021;94(1117):20200873. doi:10.1259/bjr.20200873

2. Tapping the potential of biology-guided radiation technology. News release. City of Hope. February 6, 2024. Accessed July 23, 2024. https://tinyurl.com/3h2es23p