Prediction of [¹⁷⁷Lu]Lu-DOTA-TATE therapy response using the absorbed dose estimated from [¹⁷⁷Lu]Lu-DOTA-TATE SPECT/CT in patients with metastatic neuroendocrine tumour

Background: Peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTA-TATE has shown efficacy in patients with metastatic neuroendocrine tumours (NETs). Personalised dosimetry is crucial to optimise treatment outcomes and minimise adverse events. In this study, we investigated the correlation between the tumour-absorbed dose (TAD) estimated from [¹⁷⁷Lu]Lu-DOTA-TATE SPECT/CT and the therapeutic response.

Method: A retrospective analysis was conducted on patients with advanced well-differentiated NETs grades 1-3 who underwent PRRT and exhibited greater uptake than liver on pre-therapeutic [⁶⁸Ga]Ga-DOTA-TOC PET/CT. Target lesions were selected based on the RECIST 1.1 and PERCIST 1.0 criteria using [¹⁷⁷Lu]Lu-DOTA-TATE SPECT/CT and pre-therapeutic contrast-enhanced CT scans. For anatomical image analysis, the sum of the longest diameter (SLD) of the target lesions was measured using the RECIST 1.1 criteria for patient-based analysis and the longest diameter (LD) of the target lesion using the RECIST-L criteria for lesion-based analysis. Standardised uptake values (SUVs) were measured on SPECT/CT images, and TADs were calculated based on the SUVs. Dosimetry was performed using a single SPECT/CT imaging time point at day 4-5 post-therapy. Statistical analyses were conducted to investigate correlations and determine the target lesion responses.

Results: Twenty patients with primary tumour sites and hepatic metastases were included. Fifty-five target lesions, predominantly located in the pancreas and liver, were analysed. The cumulative TAD (lesion-based analysis: r = 0.299-0.301, p = 0.025-0.027), but not the cycle 1 SUV (lesion-based analysis: r = 0.198-0.206, p = 0.131-0.147) or cycle 1 TAD (lesion-based analysis: r = 0.209-0.217, p = 0.112-0.126), exhibited a significant correlation with the change in LD of the target lesion. Binary logistic regression analysis identified the significance of the cumulative TAD in predicting disease control according to the RECIST-L criteria (odds ratio = 1.031-1.051, p = 0.024-0.026).

Conclusions: The cumulative TAD estimated from [¹⁷⁷Lu]Lu-DOTA-TATE SPECT/CT revealed a significant correlation with change in LD, which was significantly higher for the cumulative TAD than for the cycle 1 SUV or TAD. A higher cumulative TAD was associated with disease control in the target lesion. However, considering the limitations inherent to a confined sample size, careful interpretation of these findings is required. Estimation of the cumulative TAD of [¹⁷⁷Lu]Lu-DOTA-TATE therapy could guide the platform towards personalised therapy.