A Prospective Observational Study to Evaluate the Effects of Long-Acting Somatostatin Analogs on 68Ga-DOTATATE Uptake in Patients with Neuroendocrine Tumors

Abstract

Patients with neuroendocrine tumors (NETs) are often treated with somatostatin analogs (SSAs) for control of symptoms and tumor growth. Such therapy could theoretically lead to misinterpretation of somatostatin receptor imaging with ⁶⁸Ga-DOTATATE PET/CT by interfering with tracer-receptor binding. Guidelines recommend an interval of 3-4 wk between the last dose and imaging. The aim of this study was to evaluate if long-acting (LA) SSA treatment changes the uptake of ⁶⁸Ga-DOTATATE in patients with NETs. Methods: From 2013 to 2016, 296 patients with, or under evaluation for, NETs were included in this prospective observational study. The effect of LA SSA on tracer uptake was evaluated in 2 main patient populations: those undergoing ⁶⁸Ga-DOTATATE PET/CT before starting LA SSA treatment and at least once afterward, and those receiving ongoing LA SSA therapy, in whom the effect of the interval between the last dose of LA SSA and the PET/CT exam was analyzed. A third, explorative, analysis was performed to evaluate if clinical disease progression, regression, or stable tumor status changed the uptake of ⁶⁸Ga-DOTATATE. In the 3 analyses, measurements of SUV_max in normal liver and tumor lesions were compared. Results: The median SUV_max in normal liver was significantly higher before treatment (8.6; interquartile range, 7.4-10.2) than after treatment initiation (6.0; 4.7-8.0) (P < 0.001). No significant changes in SUV_max were seen in tumor lesions after treatment initiation. No significant differences in SUV_max were found in normal liver or tumor lesions dependent on the interval between last dose of LA SSA and PET/CT. Conclusion: Treatment with LA SSA does not change SUV_max in tumor lesions, whereas SUV_max in normal liver is significantly lower after treatment. The findings have implications for interpretation of ⁶⁸Ga-DOTATATE PET/CT for response assessment after SSA therapy and for guidelines on discontinuation of treatment before PET/CT.

Keywords: 68Ga-DOTATATE; PET/CT; neuroendocrine tumor; somatostatin analogs; somatostatin receptor imaging.

FIGURE 1.

Box plots of uptake before and after initiation of LA SSA treatment: SUV_max in normal liver (P < 0.001) (A), average SUV_max in tumor (P = 0.33) (B), highest SUV_max in tumor (P = 0.15) (C), and average SUV_max tumor-to-liver ratio (P = 0.01) (D). P < 0.05 on Wilcoxon rank testing was considered statistically significant.

FIGURE 2.

Examination of same patient with ⁶⁸Ga-DOTATATE/PET/CT before (A) and after (B) treatment with LA SSA. At top are coronal maximum-intensity projections of PET images; at bottom, images at same axial plane as PET images.

FIGURE 3.

Box plots of uptake at various intervals since initiation of last dose of LA SSA: SUV_max in normal liver (P = 0.88) (A) and average SUV_max in tumor (P = 0.68) (B). P < 0.05 on Kruskal–Wallis testing was considered statistically significant. No significant differences dependent on time since injection were found.

FIGURE 4.

Box plots of differences (∆) in highest SUV_max in tumor (P = 0.022) (A) and in average SUV_max in tumor (P = 0.004) (B) related to disease status at second examination with ⁶⁸Ga-DOTATATE/PET/CT. P < 0.05 on Kruskal–Wallis testing was considered statistically significant. Small significant differences were found.