Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models

• Published in: Contrast media and molecular imaging 2017-01, Vol.2017 (2017), p.1-10
• Main Authors: Vali, Reza, Shammas, Amer, Besanger, Travis, Baruchel, Sylvain, Wu, Bing, Do, Trevor, Ganguly, Milan, Komal, Teesha, McKee, Trevor, Scollard, Deborah A., Vines, Douglass C., Zhang, Libo, Alexander, Natasha
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antitumor activity; Autoradiography; Bone marrow; Cancer therapies; Cell culture; Cell Line, Tumor; Chelating Agents; Chemotherapy; Correlation analysis; Deoxyribonucleic acid; DNA; Drug dosages; Gallium; Gallium Radioisotopes - pharmacokinetics; Gallium Radioisotopes - therapeutic use; Gene expression; Growth inhibition; Heterocyclic Compounds, 1-Ring; Heterografts; Humans; Imaging; Immunohistochemistry; Lutetium - therapeutic use; Lutetium isotopes; Medical imaging; Mice; Neuroblastoma; Neuroblastoma - diagnostic imaging; Neuroblastoma - radiotherapy; Neuroendocrine tumors; Norepinephrine; Norepinephrine transporter; Nuclear medicine; Oncology; Patients; Pediatrics; Positron emission; Positron emission tomography; Positron-Emission Tomography - methods; Radioisotopes - therapeutic use; Radiopharmaceuticals - pharmacokinetics; Receptors, Somatostatin - analysis; Receptors, Somatostatin - metabolism; Single photon emission computed tomography; Somatostatin; Somatostatin receptors; Therapy; Tomography; Tumors; Xenografts; Xenotransplantation
• ISSN: 1555-4309; 1555-4317
• DOI: 10.1155/2017/9481276

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 micro-PET 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-DOTA-TATE (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.