Cumulative Absorbed Dose and Successive Cyclic Reduction in Absorbed Dose Predict Response to ¹⁷⁷ Lu-DOTATATE in Neuroendocrine Tumors

Journal article

The aim of this study was to use image-derived dose metrics to predict the radiologic response of neuroendocrine tumors treated with [177Lu]Lu-DOTATATE. Particular focus was given to the evaluation of cyclic changes in absorbed dose per administered activity (AD/AA) as a potential prognostic factor. Methods: Data from 73 patients enrolled in the multicenter OZM-067 trial (NCT02743741) were analyzed. All patients who received 4 cycles of [177Lu]Lu-DOTATATE and underwent SPECT/CT imaging at 3 time points after each treatment were included. Tumor dosimetry was based on semiautomatic adaptive-threshold segmentations and recovery coefficient-based partial-volume correction; tumors smaller than 10 cm³ were excluded. If multiple tumors were segmented per patient, the mean absorbed dose (AD) and AD/AA were recorded at each cycle. Radiologic response was assessed using RECIST 1.1 criteria. Results: A significant decrease in AD/AA across cycles was observed, with a median decline of approximately 10% per cycle. Within this cohort, 28 patients had a partial response, 33 had stable disease, and 12 experienced disease progression. Responders exhibited a higher mean cumulative AD and greater decreases in AD/AA in successive cycles when compared with nonresponders. These metrics were uncorrelated predictors of response (P = 0.64). Notably, all 8 patients with an AD of at least 100 Gy and a decrease of at least 50% in AD/AA between cycles 1 and 4 were responders. Quantitative models combining AD and changes in AD/AA achieved an area under the receiver-operating-characteristic curve of 0.78. Conclusion: Both AD and changes in AD/AA were independently associated with radiologic response to [177Lu]Lu-DOTATATE in patients with neuroendocrine tumors. The consistent decrease in AD/AA over a course of therapy suggests a potential imaging biomarker that could inform adaptive treatment strategies, which should be further evaluated in a prospective setting and considered when designing dosimetry-guided [177Lu]Lu-DOTATATE trials.

Authors: Macsuka, MJ; Driscoll, B; Yeung, IWT; Publicover, J; Metser, U

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Society of Nuclear Medicine and Molecular Imaging
• Journal: Journal of Nuclear Medicine
• Pages: jnumed.125.271039-jnumed.125.271039
• Publication date: 2026-01-29
• Acceptance date: 2025-12-30
• DOI: 10.2967/jnumed.125.271039
• EISSN: 2159-662X
• ISSN: 0161-5505
• Language: English
• Keywords: Cumulative dose; Absorbed dose; Response Evaluation Criteria in Solid Tumors; Neuroendocrine tumors; Progressive disease; Radioimmunotherapy; Dosimetry; Dose–response relationship