PET/CT with 18F-FDG and 68Ga-DOTATOC in pulmonary carcinoid imaging

Abstract: Background: PET/CT, positron emission tomography combined with computed tomography, with 18F-FDG (2-deoxy-2-[18F]fluoro-D-glucose) is well established in oncological imaging. Pulmonary carcinoid tumours may have metabolic activity, making them available for PET/CT imaging with 18F-FDG. Positron-emitting isotope-labelled somatostatin analogues, such as DOTATOC (DOTA = 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid, TOC = D-Phe1-Tyr3-Octreotide), have during the last years become more widely available for imaging of abdominal neuroendocrine neoplasms by PET. 68Ga -DOTATOC PET is recommended by the latest version of the National Care Program for neuroendocrine abdominal tumours (2018) in Sweden, for the imaging work-up of patients with suspected or verified abdominal neuroendocrine tumour, https://www.cancercentrum.se/samverkan/cancerdiagnoser/neuroendokrina-buktumorer/vardprogram/gallande-vardprogram/, [cited 2019 aug 15]. Pulmonary carcinoid tumours exhibit somatostatin receptors (SSTRs). PET/CT with 68Ga-DOTATOC presents the possibility of a more accurate evaluation of respiratory tract neoplasms such as pulmonary carcinoids. Purpose: To differentiate pulmonary carcinoids from pulmonary hamartomas and typical from atypical pulmonary carcinoids by means of 18F-FDG PET and/or 18F-FDG PET and 68Ga -DOTATOC PET. Study I showed that 18F-FDG PET/CT can distinguish pulmonary carcinoids from pulmonary hamartomas with a negative predictive value (NPV) of 92% by applying a partial volume effect corrected for the maximum standardised uptake value (SUVmax ) of 1.5 as a cutoff. However, these 18F-FDG PET measurements do not allow for the distinction between atypical and typical pulmonary carcinoids. Study II evaluated 18F-FDG PET/CT and 68Ga-DOTATOC PET/CT scans in pulmonary carcinoids in correlation with SSTR expression profiles, tumour proliferation and pulmonary carcinoid subtype (typical / atypical). No correlation was found between 18F-FDG or 68Ga-DOTATOC tracer uptake in PET/CT and tumour subtype (typical pulmonary carcinoid / atypical pulmonary carcinoid). Correlation between 68Ga-DOTATOC and 18F-FDG uptake, using the tumour-to-normal-liver ratio, and immunohistochemistry in tumours, regarded as somatostatin receptor subtype 2 (or 2 and 5), was investigated. Between 68Ga-DOTATOC and 18F-FDG uptake, an inverse imaging phenotype was shown in relation to the SSTR expression profile with high 68Ga-DOTATOC accumulation and low 18F-FDG uptake in carcinoids positive for SSTR subtypes 2 (or 2 and 5) and conversely, low 68Ga-DOTATOC accumulation and high 18F-FDG uptake in carcinoids negative for SSTR subtypes 2 (or 2 and 5). 68Ga-DOTATOC uptake was significantly higher for tumours expressing SSTR subtypes 2 (or 2 and 5) as compared to the tumours not expressing SSTR subtypes 2 (or 2 and 5). 18F-FDG uptake and Ki-67 (a marker for cell proliferation) labelling index were significantly higher for tumours not expressing SSTR subtypes 2 (or 2 and 5) as compared to the other subgroups. 68Ga-DOTATOC and 18F-FDG uptake were found to reflect tumour grading (as formulated in the study), based on Ki-67 labelling index. Conclusions: It was possible to differentiate pulmonary carcinoids from hamartomas using PET measurements of the 18F-FDG-uptake in the tumours, corrected for partial volume effect. Clinically more aggressive, atypical pulmonary carcinoids could not be differentiated from typical pulmonary carcinoids by neither 18F-FDG PET/CT nor by 68Ga-DOTATOC PET/CT. In pulmonary carcinoid tumours, an increased 68Ga-DOTATOC uptake reflected somatostatin receptor subtype 2 and 5 expression. The genotypes in pulmonary carcinoids were reflected in the imaging phenotypes with inverse 68Ga-DOTATOC and 18F-FDG accumulation patterns related to the tumour somatostatin receptor profile and proliferative activity.