O-13 Re-Treatment With Lu-177 in a Metastatic Functioning Neuroendocrine Tumor of Probable Gastrointestinal Origin: Clinical Course Following First-Line Therapy With Somatostatin Analogues and PRRT

Abstract Introduction Well-differentiated metastatic functioning neuroendocrine tumors (NETs), particularly of gastrointestinal origin, pose diagnostic and therapeutic challenges. Although often slow growing, they may follow an unpredictable course. Somatostatin analogues (SSAs) are the first-line therapy, while peptide receptor radionuclide therapy (PRRT) with Lu-177-DOTATATE has become an established second-line option in progressive disease. Here, we present a case of functioning NET with liver, mesenteric and bone involvement, showing favorable long-term response to initial PRRT and later re-treatment upon biochemical progression. Clinical Case A 2019 initial evaluation revealed multiple hepatic metastases, mesenteric nodules and bone lesions. Octreoscan confirmed somatostatin receptor expression. Diagnosis: functioning NET, likely gastrointestinal origin, stage IV. The patient was started on lanreotide 120 mg/month. In 2020, PET-Ga68 demonstrated progressive disease; liver biopsy confirmed well-differentiated G1 NET (low Ki-67). The NET tumor board recommended PRRT with Lu-177-DOTATATE. Post-therapy follow-up showed biochemical improvement and radiologic stabilization. PET-Ga68 in 2022 and CT in 2023 confirmed partial tumor shrinkage with stable disease. In April 2024, PET-Ga68 revealed persistent somatostatin-avid metastases with minor radiologic progression. Despite this, the patient remained asymptomatic, with preserved renal and bone marrow functions. In early 2025, the multidisciplinary team proposed PRRT re-treatment due to favorable profile: G1 tumor, strong receptor expression, no clinical deterioration and a progression-free interval 3 years. A dosimetric evaluation was performed, and a new Lu-177 cycle was scheduled. This decision was supported by international guidance and by increasing real-world experience suggesting that PRRT re-treatment may be a safe and effective option in selected patients. Conclusion This case underscores the importance of multidisciplinary management in advanced NETs and highlights the potential of PRRT not only in initial treatment but also as re-treatment in selected patients. Key criteria for re-treatment include sustained receptor expression, clinical stability, organ function preservation, and significant time since first PRRT. Re-treatment with Lu-177 should be considered a valuable tool in the therapeutic arsenal for NETs, especially when tumor biology and patient profile remain favorable over time. This case also illustrates the relevance of integrating functional imaging and dosimetric evaluation into personalized decision-making pathways. Individualized assessment and adherence to updated guidelines are essential for optimizing outcomes.