Correlation of somatostatin receptor-2 expression with gallium-68-DOTA-TATE uptake in neuroblastoma xenograft models

Abstract

Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as68Ga-DOTA-TATE and177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with68Ga-DOTA-TATE uptake and177Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro- PET imaging and autoradiography, a higher uptake of68Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and68Ga-DOTA-TATE uptake in CHLA-15 tumors.With a low dose of177Lu-DOTATATE (20MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET), amolecular target for131I-MIBG therapy, low123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with68Ga-DOTA-TATE uptake and antitumor efficacy of177Lu-DOTA-TATE.68Ga-DOTA-TATE PET is superior to123I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for177Lu-DOTA-TATE therapy.