Comparison of Two PET Methods for Accurate Diagnosis of Marginal Zone Lymphoma: Does a New Contrast Agent Offer Advantages?

Marginal zone lymphoma (MZL) is one of the so-called indolent (slow-growing) non-Hodgkin lymphomas. This disease affects B cells—a specific type of white blood cell. MZL often develops gradually and is usually not detected until an advanced stage, when enlarged lymph nodes or general symptoms become apparent. Precise diagnostic assessment of the extent of the disease, including staging, is crucial for treatment decisions. As a standard procedure, positron emission tomography combined with computed tomography (PET/CT) using the radioactively labeled substance [¹⁸F]FDG is performed. During this procedure, the patient is administered a weakly radioactive sugar compound (FDG) intravenously. This sugar accumulates particularly in cells with high energy consumption—typically cancer cells. Specialized imaging (PET/CT) can then reveal where in the body particularly large amounts of FDG are being taken up. The procedure thus helps identify tumor foci and assess the extent of the disease. However, this method has its limitations in the case of MZL, as not all tumor cells take up sufficient amounts of FDG. [⁶⁸Ga]Ga-PentixaFor is a new radioactively labeled contrast agent that specifically recognizes the surface protein CXCR4 on cells. This surface marker is particularly common on white blood cells, including cells of the MZL. As a result, [⁶⁸Ga]Ga-PentixaFor could visualize tumor foci more reliably than the previous method.

The goal of the LYMFOR study is to assess how well the new imaging method— [⁶⁸Ga]Ga-PentixaFor-PET/CT—compared to the current standard method ([¹⁸F]FDG-PET/CT)—is suitable for visualizing an LN in the body. To this end, untreated patients with LNs are participating in the study.

The study is designed so that each patient undergoes both imaging methods, but in a random order. This is known as a “crossover design.” This means that some patients will first undergo the new examination, while others will first undergo the standard examination—after a short break, the other method will then be performed for each patient. Which method is performed first is decided at random—this is called randomization.

The goal of this design is to enable the most objective comparison possible: Since each person undergoes both procedures, it is possible to determine directly which method provides more or more accurate information about the lymphoma. This will help determine whether the new PET/CT scan with [68Ga]Ga-PentixaFor detects the lymphoma better than the previous standard method. After both examinations, the results are compared. The evaluation will assess not only how many affected areas were found in the body, but also how well the images can be interpreted and whether there are differences in the safety or tolerability of the two methods. Overall, this study aims to test a new, potentially better method for diagnosing and evaluating marginal zone lymphoma—before treatment even begins.

Eligible participants are women and men aged 18 and older who have been diagnosed with marginal zone lymphoma and have not yet received any treatment. Patients with acute infections, severe comorbidities, or an ongoing pregnancy are excluded. Recent treatment with anticancer drugs or other PET/CT scans prior to the start of the study are also exclusion criteria.

Facts 1. Disease: Marginal zone lymphoma (MZL). 2. Cancer characteristics: Newly diagnosed, untreated. 3. What the study investigates: Comparison of two imaging techniques: [¹⁸F]FDG-PET/CT vs. [⁶⁸Ga]Ga-PentixaFor-PET/CT. 4. Study objective: Improved detection of tumor foci in the body. 5. Study duration: Approx. 6 months; both PET/CT scans are performed in close succession. 6. Study characteristics: International, multicenter Phase 3 study; sequential assignment; crossover design: both treatments are administered in an open-label manner (the treatment is known to both patients and physicians).