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

Macsuka MJ., Driscoll B., Yeung IWT., Publicover J., Metser U., Juergens R., Myrehaug SD., Laidley D., Wong RK., McGowan DR., Vallis KA.

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.

DOI

10.2967/jnumed.125.271039

Type

Journal article

Publication Date

2026-01-29T00:00:00+00:00

Keywords

[177Lu]Lu-DOTATATE, dosimetry, neuroendocrine tumors, radiopharmaceutical therapy, treatment response

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