Pre-treatment In-pentetreotide SPECT/CT vs. baseline Lu-DOTATATE SPECT/CT: are there differences in lesion uptake and detectability?

Background: In-pentetreotide imaging remains used for pre-treatment screening in peptide receptor radionuclide therapy (PRRT) in regions where somatostatin receptor (SSTR)-PET tracers are clinically unavailable. Post-treatment Lu-DOTATATE imaging at the first PRRT cycle serves as a baseline for response assessment on subsequent post-treatment imaging, paralleling the role of pre-treatment In-pentetreotide imaging. However, differences between these SSTR scans have not been reported. This study aims to compare In-pentetreotide and Lu-DOTATATE imaging, focusing on lesion uptake and numbers.

Methods: This retrospective, single-center study included patients with neuroendocrine tumors (NETs) who underwent PRRT at our hospital. Planar and SPECT/CT of pre-treatment In-pentetreotide and post-treatment Lu-DOTATATE imaging at the first PRRT cycle were analyzed. For visual analysis, the number of SSTR-positive (Krenning score ≥ 2) lesions was counted for each tracer. For quantitative analysis, up to three representative SSTR-positive lesions per patient were selected, and the maximum standardized uptake value (SUVmax) and tumor-to-background (T/B) ratio were measured. Wilcoxon signed-rank test was used to compare lesion counts and uptake parameters.

Results: A total of 10 patients and 28 lesions were included. The median interval between In-pentetreotide and Lu-DOTATATE imaging was 43 days. Lu-DOTATATE imaging detected significantly more lesions than In-pentetreotide on both planar (median 10 vs. 6.5 lesions, p = 0.009) and SPECT/CT (median 13.5 vs. 8 lesions, p = 0.014). Lesion uptake was higher with Lu-DOTATATE, with SUVmax (median 4.5 vs. 2.9, p < 0.001) and T/B ratios (median 13.9 vs. 4.7, p < 0.001). Sub-centimeter lesions accounted for most of the additional detections on Lu-DOTATATE SPECT/CT.

Conclusion: Baseline Lu-DOTATATE imaging demonstrated higher lesion uptake and detected more lesions compared to pre-treatment In-pentetreotide imaging. Careful interpretation of baseline Lu-DOTATATE imaging is essential to avoid misinterpreting the increased number of detected lesions as disease progression. Screening with In-pentetreotide imaging may underestimate treatable lesions by PRRT, particularly when planar imaging alone is used, highlighting the need for SSTR PET in pre-treatment evaluation.