Heterogeneity of SSTR2 expression assessed by 68 Ga-DOTATOC PET/CT using coefficient of variation in patients with neuroendocrine tumors

High levels of somatostatin receptor type 2 (SSTR2) is a prerequisite for therapy with unlabeled or labeled somatostatin analogues. However, it is still unclear how the heterogeneity of SSTR2 expression could 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 Ga-peptides in the evaluation and quantification of the heterogeneity of SSTR2 expression within primary and metastatic lesions of patients with neuroendocrine tumors. Thirty-eight patients with pathologically proven neuroendocrine tumors who underwent Ga-DOTATOC-PET/CT were studied. Primary tumors were localized in the gastroenteropancreatic, bronchopulmonary and other anatomical districts in 25, 7 and 6 patients, respectively. Malignant lesions were segmented using an automated contouring program and a threshold of SUV> 2.5 or in the case of liver lesions a threshold of 30% of the SUV The imaging parameters SUVmean, CoV, SUV , RETV (receptor expressing tumor volume) and TLRE (total lesion receptor expression) of each lesion were obtained. SUVmean, CoV, SUV were also obtained in representative volumes of normal liver, spleen as well as in the whole pituitary gland. A total of 107 lesions were analyzed including 35 primary tumors, 32 metastatic lymph nodes and 40 distant metastases. Average CoV values were 0.49±0.20 in primary tumors, 0.57±0.26 in lymph node metastases and 0.44±0.20 in distant metastases. CoV values in malignant lesions were up to 4-fold higher than those of normal tissues (p≤0.0001). Among malignant lesions the highest CoV value was found in bone metastases (0.68±0.20) and was significantly greater than that of primary lesions ( = 0.01) and liver metastases (0