111In-Pentetreotide Scintigraphy Versus 68Ga-DOTATATE PET: Impact on Krenning Scores and Effect of Tumor Burden

Eligibility for somatostatin receptor (SSTR) radionuclide therapy uses the qualitative Krenning score based on In-111-pentetreotide planar scintigraphy as was performed in the NETTER-1 trial. The purpose of this study was to determine the effect of using SSTR PET-based Krenning score in comparison to In-111-pentetreotide. Methods: This was a post hoc head-to-head comparison of Ga-68-DOTATATE-based and In-111-pentetreotide-based Krenning scores in 150 patients included in a prospective phase 2 study (NCT01967537). Patients were imaged using Ga-68-DOTATATE PET/CT, In-111-pentetreotide planar scintigraphy, and SPECT/CT within 1 wk. SSTR ligand uptake was graded using the Krenning score independently by 3 readers. Results: The detection rate of SSTR-expressing disease (Krenning scores 2-4) was 23%, 38%, and 72% with planar imaging, SPECT, and SSTR PET, respectively. The Krenning score was higher with SSTR PET (2.71 +/- 1.74) than with planar imaging (0.75 +/- 1.37; P < 0.001) or SPECT (1.23 +/- 1.57; P < 0.001). In patients with a Krenning score of at least 3 on SSTR PET, the detection rate of planar imaging and SPECT was lower for lesions smaller than 2 cm than lesions 2 cm or larger: 15% and 24% versus 78% and 89%, respectively (P < 0.001). For lesions larger than 5 cm, Krenning scores between SSTR PET and In-111-pentetreotide were nearly equivalent. Lesion size did not have an impact on SSTR PET Krenning scores. Interreader agreement was higher for SSTR PET than for planar imaging or SPECT (0.79 vs. 0.67 and 0.50, respectively). Conclusion: SSTR PET results in higher Krenning scores than In-111-pentetreotide, particularly when lesions measured 2 cm or less. Small lesion size resulted in low Krenning scores using In-111-pentetreotide, but lesion size did not affect SSTR PET-based Krenning scores. The results of the NETTER-1 trial cannot be directly applied to patients with small lesions. Further study of peptide receptor radionuclide therapy in patients with small lesions negative on In-111-pentetreotide imaging and positive on SSTR PET is warranted.