Heterogeneity of SSTR2 Expression Assessed by 68Ga-DOTATOC PET/CT Using Coefficient of Variation in Patients with Neuroendocrine Tumors

Abstract

High levels of somatostatin receptor subtype 2 (SSTR2) are a prerequisite for therapy with unlabeled or labeled somatostatin analogs. However, it is still unclear how the heterogeneity of SSTR2 expression may affect tumor response to therapy. The aim of our study was to test the ability of an imaging parameter such as coefficient of variation (CoV) derived from PET/CT with ⁶⁸Ga-peptides in the evaluation and quantification of the heterogeneity of SSTR2 expression within primary and metastatic lesions of patients with neuroendocrine tumors. Methods: Thirty-eight patients with pathologically proven neuroendocrine tumors who underwent ⁶⁸Ga-DOTATOC PET/CT were studied. Primary tumors were localized in the gastroenteropancreatic, bronchopulmonary, and other anatomic districts in 25, 7, and 6 patients, respectively. Malignant lesions were segmented using an automated contouring program and an SUV threshold of more than 2.5 or, in the case of liver lesions, a threshold of 30% of the SUV_max The imaging parameters SUV_mean, CoV, SUV_max, receptor-expressing tumor volume, and total lesion receptor expression were obtained for each lesion. SUV_mean, CoV, and SUV_max were also obtained for representative volumes of normal liver and spleen, as well as for the whole pituitary gland. Results: In total, 107 lesions were analyzed, including 35 primary tumors, 32 metastatic lymph nodes, and 40 distant metastases. Average CoVs were 0.49 ± 0.20 for primary tumors, 0.57 ± 0.26 for lymph node metastases, and 0.44 ± 0.20 for distant metastases. The CoVs of malignant lesions were up to 4-fold higher than those of normal tissues (P ≤ 0.0001). Among malignant lesions, the highest CoV was found for bone metastases (0.68 ± 0.20), and it was significantly greater than that of primary lesions (P = 0.01) and liver metastases (P < 0.0001). On the other hand, the lowest CoV was found for liver lesions (0.32 ± 0.07), probably because of the high background uptake. Conclusion: Our findings indicate that the heterogeneity of uptake, reflecting that of SSTR2, varies with the type and site of malignant lesions as assessed by CoVs obtained from ⁶⁸Ga-DOTATOC PET/CT scans. These observations may be related to different biologic characteristics of tumor lesions in the same patient-differences that may affect their response to treatment with both labeled and unlabeled somatostatin analogs.

Keywords: 68Ga-peptide PET/CT; coefficient of variation; heterogeneity; neuroendocrine tumors; somatostatin receptor 2.