Author/Authors :
Zhang, Libo Hospital for Sick Children - Toronto, Canada , Vines, Douglass C University Health Network - Toronto, Canada , Scollard, Deborah A University Health Network - Toronto, Canada , McKee, Trevor University Health Network - Toronto, Canada , Komal, Teesha University Health Network - Toronto, Canada , Ganguly, Milan University Health Network - Toronto, Canada , Do, Trevor University Health Network - Toronto, Canada , Wu, Bing Hospital for Sick Children - Toronto, Canada , Alexander, Natasha Hospital for Sick Children - Toronto, Canada , Vali, Reza Hospital for Sick Children - Toronto, Canada , Shammas, Amer Hospital for Sick Children - Toronto, Canada , Besanger, Travis Center for Probe Development and Commercialization - Hamilton, Canada , Baruchel, Sylvain Hospital for Sick Children - Toronto, Canada
Abstract :
Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-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 with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in
neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From microPET imaging and autoradiography, a higher uptake of 68Ga-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 and 68Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177Lu-DOTATATE (20 MBq/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), a molecular target for 131I-MIBG therapy,
low 123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68Ga-DOTA-TATE uptake and antitumor efficacy of 177Lu-DOTA-TATE. 68Ga-DOTA-TATE PET is superior to 123I-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 for 177Lu-DOTA-TATE therapy.
Keywords :
Xenograft , NB , TATE , DOTA-NOC
