Correlation of somatostatin receptor PET/CT imaging features and immunohistochemistry in neuroendocrine tumors of the lung: a retrospective observational study

Abstract

Purpose To correlate somatostatin receptor (SSTR) and proliferative activity profile (SSTR2, SSTR5, Ki-67) at immunohistochemistry (IHC) with SSTR-PET/CT imaging features in a retrospective series of lung neuroendocrine tumors (NET). Proliferative activity by Ki-67 and 18F-FDG-PET/CT parameters (when available) were also correlated. Methods Among 551 patients who underwent SSTR-PET/CT with 68Ga-DOTA-somatostatin analogs (SSA) between July 2011 and March 2020 for lung neuroendocrine neoplasms, 32 patients with a confirmed diagnosis of NET were included. For 14 of them, 18F-FDG-PET/CT was available. PET/CT images were reviewed by qualitative and semi-quantitative analyses. Immunohistochemistry for SSTR2, SSTR5, and Ki-67 was assessed. Inferential analysis was performed including kappa statistics and Spearman’s rank correlation test. Results Definitive diagnosis consisted of 26 typical carcinoids-G1 and six atypical carcinoids-G2. Positive SSTR2-IHC was found in 62.5% of samples while SSTR5-IHC positivity was 19.4%. A correlation between SSTR2-IHC and SSTR-PET/CT was found in 24/32 cases (75.0%, p = 0.003): 20 were concordantly positive, 4 concordantly negative. For positive IHC, 100% concordance with SSTR-PET/CT (both positive) was observed, while for negative IHC concordance (both negative) was 33.3%. In 8 cases, IHC was negative while SSTR-PET/CT was positive, even though with low-grade uptake in all but one. A significant correlation between SUVmax values at SSTR-PET/CT and the SSTR2-IHC scores was found, with low SUVmax values corresponding to negative IHC and higher SUVmax values to positive IHC (p = 0.002). Conclusion This retrospective study showed an overall good agreement between SSTR2-IHC and tumor uptake at SSTR-PET/CT in lung NETs. SSTR-PET/CT SUVmax values can be used as a parameter of SSTR2 density. Within the limits imposed by the relatively small cohort, our data suggest that SSTR2-IHC may surrogate SSTR-PET/CT in selected lung NET patients for clinical decision making when SSTR-PET/CT is not available.

Somatostatin Receptor-Directed PET/CT for Therapeutic Decision-Making and Disease Control in Patients Affected With Small Cell Lung Cancer

“…This is in line with a head-to-head comparison between [ 68 Ga]DOTATOC PET and CT, which enrolled a mixed cohort of digestive and pulmonary NENs and also reported on superior accuracy for bone lesions by the molecular imaging component 23 . As a possible explanation, skeletal alterations may appear rather subtle and thus may be more likely missed on morphological imaging 22,23 . Nonetheless, in patients affected with SCLC, hybrid imaging achieves synergistic diagnostic accuracy, thereby providing a complementary, whole-body readout of the current disease status.…”

“…18,20 Such highly aggressive NEN types, however, are characterized by varying expression of SSTR, irrespective if primaries are located in the digestive 21 or pulmonary system. 7,22 In our study, SSTR PET was superior relative to CT for assessing tumor burden in the skeleton. This is in line with a head-to-head comparison between [ 68 Ga] DOTATOC PET and CT, which enrolled a mixed cohort of digestive and pulmonary NENs and also reported on superior accuracy for bone lesions by the molecular imaging component.…”

“… 23 As a possible explanation, skeletal alterations may appear rather subtle and thus may be more likely missed on morphological imaging. 22 , 23 Nonetheless, in patients affected with SCLC, hybrid imaging achieves synergistic diagnostic accuracy, thereby providing a complementary, whole-body readout of the current disease status.…”

The potential application of MR-derived ADCmin values from 68Ga-DOTATATE and 18F-FDG dual tracer PET/MR as replacements for FDG PET in assessment of grade and stage of pancreatic neuroendocrine tumors

“…However, since SSTR expression is lower on high-grade poorly differentiated NETs, 18 F-FDG PET imaging is more reliable for evaluating these tumors [6]. 68 Ga-DOTANOC PET-based SUVmax values can serve as a reflection of SSTR2 density [7], whereas 18 F-FDG PET uptake values correspond to increases in metabolic activity at the cellular and tissue levels. Previous research efforts have demonstrated the complementary value of combining quantitative parameters derived from 68 Ga-DOTA-peptides and 18 F-FDG PET imaging analyses when evaluating PNET aggressiveness and conducting prognostic assessments [8,9].…”

The potential application of MR-derived ADCmin values from 68Ga-DOTATATE and 18F-FDG dual tracer PET/MR as replacements for FDG PET in assessment of grade and stage of pancreatic neuroendocrine tumors

“…Currently, 68 Ga-DOTA peptide-based imaging approaches are the gold standard used for assessing welldifferentiated NETs exhibiting high levels of somatostatin receptor (SSTR) density, [5] However, since SSTR expression is lower on high-grade poorly differentiated NETs, 18 F-FDG PET imaging is more reliable for evaluating these tumors. [6] 68 Ga-DOTANOC PET-based SUVmax values can serve as a re ection of SSTR2 density, [7] whereas 18 F-FDG PET uptake values correspond to increases in metabolic activity at the cellular and tissue levels. Previous research efforts have demonstrated the complementary value of combining quantitative parameters derived from 68 Ga-DOTA-peptides and 18 F-FDG PET imaging analyses when evaluating PNET aggressiveness and conducting prognostic assessments.…”