Assessing Targeted PET Imaging for Advanced Rectal Cancer

The use of Cu 64 anti-CEA M5A as a PET imaging agent for advanced rectal cancer can potentially improve treatment efficacy and reduce unnecessary interventions, according to Jeffrey Wong, MD, and findings presented at the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting.

Cu 64 anti-CEA M5A offers several advantages over traditional imaging methods like MRI and CT scans. Firstly, its ability to scan the entire body provides a comprehensive assessment of disease spread, potentially identifying metastases that may be missed by other techniques. Secondly, the agent's specificity for carcinoembryonic antigen (CEA), a protein often overexpressed in rectal cancer, enhances its ability to accurately detect and localize tumor sites.

Early data from the study indicate that Cu 64 anti-CEA M5A has significant potential for improving the management of advanced rectal cancer. According to Wong, a professor of radiation oncology at City of Hope Medical Center, the agent has demonstrated its ability to identify disease before therapy, assess tumor response, guide treatment decisions, and potentially reduce unnecessary surgery.

While promising results were seen in an initial study evaluating this PET imaging agent in advanced rectal cancer, the trial warrants further investigation. Experts aim to focus on expanding the patient population, comparing Cu 64 anti-CEA M5A to other imaging modalities, and exploring its potential for guiding therapy selection and predicting outcomes.

In an interview with Targeted Oncology^TM, Wong further discussed the potential and future directions of Cu 64 anti-CEA M5A as a PET imaging agent for advanced rectal cancer.

GI Cancer : © SciePro - stock.adobe.com

Targeted Oncology: Can you discuss the rationale for assessing this PET imaging agent in the treatment of patients with advanced rectal cancer?

Wong: To optimize therapy for the treatment of most cancers, including rectal cancer, we need to know where the cancer is before we design and initiate therapies. So imaging is a very important part of that. Any new imaging approach or imaging agent that could potentially improve upon our ability to detect disease and identify where that disease within the body is of interest to us.

Rectal cancer is a gastrointestinal cancer that makes carcinoembryonic antigen, known as CEA. This particular agent is a monoclonal antibody that has been engineered and developed at City of Hope that recognizes CEA. This particular agent was radiolabeled with a radioisotope called Cu 64. That allows us to do CAT imaging. After injection of the antibody, the antibody targets the CEA in the rectal cancer and allows us the potential to identify sites of where the rectal cancer is, again, prior to initiating any kind of therapy

What advantages might this agent offer compared with other imaging modalities in this population?

Most of the imaging modalities, at least at this institution for rectal cancer, have focused primarily on the pelvic region. MRI scan is important, as well as CT scan. CT scans do sometimes go beyond the pelvic region in terms of staging, but this particular approach with the radiolabeled anti-CEA antibodies, a PET scan, screens the entire body. What we wanted to determine was whether this had the potential to detect disease outside the areas that are normally scanned.

What do the current data show about the potential impact of this agent in patients with advanced rectal cancer?

The study was designed first for patients with locally advanced rectal cancer, most of whom did not have any known sites of metastatic disease. This with the patients were scanned prior to therapy. Therapy is, for most patients with local locally advanced rectal cancer, chemotherapy, radiation therapy, and then surgery. This study was designed to do a radiolabeled or Cu 64 anti-CEA PET scan prior to radiation therapy and chemotherapy and after radiation therapy, but prior to surgery. The objectives were to determine how this agent could identify disease before therapy, and could it also determine tumor response after therapy?

The first scan wanted to determine whether it could identify disease. This is a pilot study, but in the number of patients we studied, all of them showed targeting of the antibody to known sites of disease patients. There were also patients where there was disease detected outside of the pelvic region. That could impact radiation field coverage, or even impact on whether a patient is appropriate for radiation therapy. That is another objective, and that was another finding.

The third finding was that we found that after radiation therapy is done, but prior to surgery, there were patients that had a positive PET scan before therapy, but then a negative PET scan after therapy, and they went on to surgery or biopsy, and that confirmed that there was absence of a tumor when the PET scan became negative. Although more work needs to be done, the potential is that this scan, especially performed prior to surgery, might help select patients who are appropriate to just continue to watch and avoid the surgery. Again, it is a bit early to reach that conclusion, but this trial was to see if there is any potential for this particular agent to do that.

Were there any other surprising findings or results reported in the study?

There were no safety issues at all; this was well tolerated, no allergic reactions or any kind of [adverse] effects with this agent. From my perspective, the agent performs surprisingly well.

In all patients studied, to have the agent target known sites of disease prior to starting a therapy was encouraging and surprising because it does not happen too often that we see that. In some patients, we did detect disease that was undetected by standard-of-care imaging, so that is also surprising and encouraging. This is a disease in lymph nodes as well as in the liver in one or two cases.

Another encouraging and surprising finding is that, so far, there is a good correlation between a negative scan and no tumor at the time of surgery. In this trial, we feel that this agent should be expanded to a large number of patients and studied further.

What are the next steps for researching this imaging agent?

The next steps are to enlarge the patient population or the number of patients that we studied with rectal cancer and begin to compare it with other forms of imaging also such as [fluorodeoxyglucose (FDG)] PET scans, which is a standard-of-care PET scan that I think most new PET agents would want to be compared to. We do have 1 case in this trial. Again, FDG PET scans are not normally done on this population at City of Hope, but we do have 1 patient on this trial where the CEA scan identified disease at the FDG PET scan did not. That 1 case will encourage us to get in a large trial and compare it with FDG PET scans.

What do you hope your colleagues take away from this trial?

This [is an] opportunity to discover new agents, and we should continue to work at finding better agents to identify disease. The second thing is that these agents that also have targeting potential that is very selective to the tumor can also be converted to therapy agents. We are doing that at City of Hope. We have this particular antibody, now labeled with a therapeutic radioactive particle called actinium-225, which is an alpha particle emitter, and it is now in phase 1 trials. We just opened another phase 1 trial that, instead of using a radioactive particle, we use an immunotherapy molecule linked to the anti-CEA antibody as a form of targeted immunotherapy for patients with CEA-expressing cancers. That is what I hope oncologists will take away. This is an exciting and emerging area.

REFERENCE:

Cu-64-anti-CEA M5A as a novel theranostics PET imaging agent pre and post neoadjuvant radiotherapy in advanced rectal cancer. Presented at: 2024 American Society for Therapeutic Radiology and Oncology Annual Meeting; September 29-October 2, 2024; Washington, DC. 1003.