<p>Imaging-based models to predict the response of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to PRRT are under development. Speakers at the <strong>2025 Society of Nuclear Medicine & Molecular Imaging (SNMMI) Annual Meeting</strong> highlighted data related to the role of imaging in PRRT.</p> <p><br></p> <p><em>Following these presentations, featured expert Jonathan R. Strosberg, MD, was interviewed by </em>Conference Reporter<em> Editor-in-Chief Tom Iarocci, MD. Clinical perspectives from Dr Strosberg on these findings are presented here.</em></p>

We conducted a study of SSTR expression in metastatic lung NETs because we noticed that a lot of grade 2 or 3 well-differentiated lung NETs were either SSTR negative or had a heterogeneous expression pattern. We found that fewer than half of patients with metastatic lung NETs would be truly eligible for PRRT if the eligibility requires reasonable SSTR expression in all tumors. So, you have to be particularly careful with lung NETs.

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There have not been very many studies telling us what percentage of patients with GEP-NETs have SSTR-negative or SSTR-heterogeneous metastatic tumors. In a recent study, we found that the majority of patients with GEP-NETs had a relatively high level of SSTR expression in all measurable tumors, but it was not 100%. The rates of SSTR negativity and heterogeneity are higher in pancreatic vs small bowel NETs and in grade 3 vs grade 1 or 2 NETs. Therefore, it is particularly important to ascertain that all tumors express SSTR in high-grade NETs and in patients with tumors originating outside of the small intestine before proceeding with PRRT.

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Some people advocate for a comparison with fluorodeoxyglucose positron emission tomography (FDG PET) to ensure that all lesions express SSTR. FDG PET can be prognostic, although I am not sure how much we gain from it in most cases. However, there are circumstances in which it could be better to match a dotatate PET with an FDG PET rather than with anatomic imaging to ascertain that all lesions express SSTR.

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A single-photon emission computed tomography (SPECT) scan can be performed after each PRRT treatment to ensure that all the tumors absorbed radioactivity and to track changes over time. It provides a quick and inexpensive measure to determine whether things are heading in the right or wrong direction after each treatment. Some people feel that you can adjust therapy based on the findings from the SPECT scans. For example, if a patient’s NETs have a great response after 2 cycles or if the disease is progressing, it may be reasonable to stop treatment at that point. However, we are still learning how ¹⁷⁷Lu-dotatate SPECT imaging can be used to make therapeutic decisions.

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In his talk titled “Progress Toward Meeting the Evidentiary Standard for Dosimetry-Guided PRRT” at the 2025 SNMMI Annual Meeting, Stephen A. Graves, PhD, DABR, concluded that we need level I evidence but we do not have it. Right now, we have very low-quality evidence. There are some studies that argue that if a patient receives more PRRT treatment cycles, they do better, and, therefore, dosimetry is recommended to maximize the number of cycles. However, these studies were not asking why some people get fewer cycles (eg, maybe their disease progressed quickly, they experienced too much toxicity, or their performance status was poor). So, there are numerous confounding issues that introduce bias to this kind of analysis. Generating high-level evidence is going to be very difficult.

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Arguably, even progression-free survival is not sufficient. If a study finds that giving more cycles of PRRT results in higher progression-free survival, that is not terribly surprising. However, what if the patient ends up experiencing more adverse events as a result of having received 6 cycles of PRRT rather than the standard 4? Maybe they now have chronic cytopenias that prevent them from getting any other treatments. Overall survival really is the gold standard, but it is not a realistic end point in this rare disease in which patients have long median survival durations.

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Questions remain regarding the tumor-absorbed dose information. For example, if a certain absorbed dose has been achieved prior to the standard 4 cycles of PRRT, do you stop there? Or, if it has not been achieved, do you keep administering it until it has been? Often, this dosimetry information is just based on a handful of tumors. In patients with metastases, we may be dealing with innumerable tumors, each with its own unique SSTR expression and radiation absorption. PRRT is not nearly as straightforward as external beam radiation therapy, and this is why I think that the external beam radiation paradigm does not work very well here.

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In another talk at the 2025 SNMMI Annual Meeting, “Patterns of Progression After PRRT,” Moein Moradpour, MD, reported that most NET lesions retain SSTR expression after progression. This is not surprising. In general, unless the disease transforms to a poorly differentiated neuroendocrine carcinoma, the tumors continue to express SSTRs after PRRT. However, that does not mean that the tumors are as radiosensitive as they were before PRRT, because they probably are not.