Dosimetry in ¹⁷⁷Lu-PRRT for Neuroendocrine Tumors: Current Concepts, Clinical Relevance and Future Perspectives

Background: Neuroendocrine tumors-are relatively rare but increasingly diagnosed malignancies originating from diffuse neuroendocrine cells, most commonly affecting the gastroenteropancreatic system. Due to their long asymptomatic development and low incidence, pose a diagnostic and therapeutic challenge for physicians. Recently, the role of nuclear medicine has been growing not only in the diagnostic stage but also in treatment. Systemic radionuclide therapy using somatostatin analogs labelled with the radioisotope lutetium-177 is becoming increasingly common in patients with advanced-stage disease. Currently, most patients receive a standard activity of therapeutic radiopharmaceuticals. Recent clinical studies provide increasing evidence of a close relationship between the absorbed radiation dose in pathological lesions and the therapeutic effect of radioisotope therapy. Internal dosimetry is used to measure the doses of ionising radiation absorbed by the patient after administration of the radiopharmaceutical. The lack of individual internal dosimetry prior to therapy means that only a small fraction of patients receive optimal doses of radioactivity, which is markedly different from external beam radiotherapy planning. Methods: A narrative literature review was conducted using the PubMed/MEDLINE and Embase databases, focusing primarily on publications from the last years. The search strategy included combinations of keywords related to peptide receptor radionuclide therapy and dosimetry, such as "Lutetium-177", "neuroendocrine tumors", "dosimetry", "PRRT", "systemic radionuclide therapy" and "artificial intelligence". Particular emphasis was placed on recent prospective clinical studies, multicenter investigations, systematic reviews and consensus documents published by major nuclear medicine societies, including the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). Seminal earlier publications considered essential for understanding the development of dosimetry concepts and clinical implementation were also included. Results: This study confirms the existence of a clinically significant dose-response relationship in ¹⁷⁷Lu-PRRT. Higher absorbed doses to tumour lesions are associated with longer progression-free survival. The lack of individualized internal dosimetry prior to therapy means that only a small proportion of patients receive optimal radiation doses. Simplified dosimetric approaches with a reduced number of imaging time points, together with emerging artificial intelligence-based tools, appear promising for reducing the complexity of the dosimetry process. Conclusions: The aim of this study was to analyse the current literature on the role of internal dosimetry in the treatment of neuroendocrine tumors using the radioisotope lutetium-177. Available data support the clinical relevance of individualized dosimetry and highlight its potential to optimize both therapeutic efficacy and treatment safety.