Due to its more targeted delivery, radioligand therapy (RLT) has potential benefits over conventional radiation therapy in gastrointestinal cancers. However, challenges remain in monitoring treatment delivery and uptake in tumors, as well as in predicting treatment response. A presentation at the 2025 ASCO Gastrointestinal Cancers Symposium outlined the challenges with theranostics and their potential solutions.

Following this presentation, featured expert Jennifer R. Eads, MD, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Clinical perspectives from Dr Eads on these findings are presented here.

The potential application of RLT is expanding, but we still lack insights into which patients will respond to treatment, how much treatment the tumors will take up, and whether the dose can be tailored to a particular patient. At the 2025 ASCO Gastrointestinal Cancers Symposium, a talk by Mekhail Anwar, MD, PhD, addressed a lot of the dosimetry-related issues and how we may be able to monitor whether a tumor is taking up treatment.

With conventional radiation therapy, you are delivering a dose to the tumor with a directed beam. Presumably, all of it is delivered, but you do not know how radiation sensitive the tumor is. What is elegant and different about RLT compared with conventional radiation therapy is that its ligand targets a tumor cell surface molecule. So, in addition to the radiation being focused on the tumor with RLT, the tumor also has to express the cell surface target for RLT to be effective. However, the expression of the cell surface target can be very heterogeneous on a given tumor; even if you know the dose of RLT that you are administering to a patient, you do not know how much of that is actually being absorbed by the tumor.

One of the things that Dr Anwar discussed during his presentation was whether there is a way to know what the actual uptake of the radioligand by the tumor is. Right now, some institutions perform single-photon emission computed tomography imaging after treatment to get a sense of whether there is uptake and, if so, how much, but that is not universally done. We also generally do not image until people complete the entirety of their therapy. So, sometimes you give a patient a 6- to 8-month treatment regimen and hope that their imaging will improve after treatment. However, 6 to 8 months is a long time to go without imaging, especially for patients with colorectal, gastric, and pancreatic cancers, so we need to have some other way to assess if treatment is on track.

A wearable device is being tested, but I think that tumor implants such as the single-particle energy transducers for radionuclide injections (SENTRI) are probably more helpful. Conceivably, you can implant multiple chips into multiple different tumors within any given patient, and the chips measure the dose that is being received by the tumor. If the SENTRI chips that are inside the tumors are measuring a high dose, then you could feel more confident that the treatment could be working vs if the chips are not picking up much. This may indicate that the tumor did not take up much of the dose, meaning that perhaps this therapy is not the best for this patient.

That, to me, is very cool, even though it is complicated in the sense of how difficult it is to execute. Tumors tend to be quite heterogeneous, so how do you know which tumors to inject the SENTRI chips into? If a patient has 100 tumors, you will not put a chip into every single one. It is probably also not practical to place 30 of these chips in a person, especially in someone with metastatic disease in the liver, lungs, and bones. That seems to be a significant intervention in a patient with metastatic disease. But this is at least a start in terms of seeing whether the chip concept can work.

In terms of linking theranostics to immunotherapy, one thing that struck me and could be interesting is whether we could use theranostics to help identify which patients have tumors expressing specific immunotherapy-targetable cell surface markers, similar to what we currently do with dotatate positron emission tomography imaging and linking it to RLT.