Quantitative SPECT imaging for predicting therapeutic response to lutetium-177 DOTATATE in neuroendocrine tumors

As the incidence of neuroendocrine tumors (NETs) increases, Lutetium-177 (Lu-177) DOTATATE targeted radionuclide therapy (TRT) has become a vital treatment strategy. However, its prolonged course makes early prediction of response challenging, and current predictive methods like dosimetry are complex. Therefore, a simpler, earlier prediction method is needed for timely treatment planning. This study aimed to investigate whether quantitative metrics from a single, initial post-therapy single-photon emission computed tomography / computed tomography (SPECT/CT) image could predict the final treatment response.

This retrospective, single-center study included 17 patients (60 tumor lesions) receiving Lu-177 DOTATATE TRT. Patients were classified into G1, G2, and G3/neuroendocrine carcinoma (NEC) groups according to the World Health Organization (WHO) 2019 classification. When multiple lesions with discrepant grades were present, the highest grade was assigned for patient-level classification. Tumor volume and maximum standardized uptake value (SUVmax) were calculated from initial and final post-therapy SPECT images using an adaptive thresholding method. Response was evaluated based on a ≥ 50% reduction in tumor volume. Statistical analyses included one-way analysis of variance (ANOVA) and Pearson's correlation.

A higher initial post-therapy SUVmax tended to correlate with a better volumetric response. In an exploratory analysis, all lesions (n = 8) with an initial post-therapy SUVmax exceeding 55 achieved a volumetric response, yielding a positive predictive value of 100% for this subgroup. The overall response rates for tumor volume and SUVmax were 71.7% and 65.0%, respectively. Additionally, G3/NEC tumors showed a significantly greater initial volume reduction than G2 tumors (p = 0.042).

Our findings suggest that the initial post-therapy SUVmax from a single SPECT/CT acquisition may serve as a promising exploratory predictor of early volumetric response to Lu-177 DOTATATE TRT. While this metric is clinically intriguing, it may reflect treatment-induced necrosis or edema rather than durable tumor control, particularly in high-grade tumors. Therefore, its relationship with long-term clinical endpoints such as progression-free survival remains to be established. This streamlined approach could contribute to personalized medicine, though further validation is required.