68Ga-DOTATOC and FDG PET Imaging of Preclinical Neuroblastoma Models

Abstract

Background/aim: Somatostatine receptors subtype 2 (SSTR2) are regarded as a potential target in neuroblastoma (NB) for imaging and promising therapeutic approaches. The purpose of this study was to evaluate and compare the SSTR2 status by (68)Ga-[tetraxetan-D-Phe1, Tyr3]-octreotide ((68)Ga-DOTATOC) positron-emission tomography (PET) and the tumour metabolic activity by (18)F-fluorodeoxyglucose (FDG) PET in different experimental models of NB.

Materials and methods: Three cell lines of human NB with different levels of expression of SSTR2 were grafted into nude mice. Animals were imaged with FDG and (68)Ga-DOTATOC and the maximum standardized uptake value (SUVmax) was determined to quantify tracer uptake. Ex vivo biodistribution of (68)Ga-DOTATOC and immunohistochemical analysis of NB xenografts were performed.

Results: Compared with FDG, the SUVmax of (68)Ga-DOTATOC uptake by the tumour was lower but the ratio to background was higher; there was a strong positive correlation between SUVmax values observed with the two tracers (r(2)=0.65). Sorting the cell lines according to uptake of FDG or (68)Ga-DOTATOC, injected activity per gram of tissue, Ki67 index or expression of SSTR2 assessed visually led to the same classification.

Conclusion: (68)Ga-DOTATOC allows preclinical imaging of NB according to the intensity of the expression of SSTR2. In contrast with what has been reported for neuroendocrine tumours, in this NB model, the (68)Ga-DOTATOC uptake was positively correlated with FDG uptake and with Ki67 index, usual markers of tumour aggressiveness. If confirmed in humans, this result would favour a theranostic application of (68)Ga-DOTATOC in NB, even in advanced stages.

Keywords: 68Ga-DOTATOC; FDG; PET; neuroblastoma model; somatostatin receptor subtype 2.