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The potential of Lu-177-octreotate as a therapeutic alternative for metastatic neuroblastoma

Konferensbidrag (offentliggjort, men ej förlagsutgivet)
Författare Arman Romiani
Johan Spetz
Emil Schüler
Wan Haiying
Ruth H. Palmer
Bengt Hallberg
Eva Forssell-Aronsson
Publicerad i 62nd Annual International Meeting Radiation Research Society, Waikoloa, HI, USA, October 16-19, 2016
Publiceringsår 2016
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för radiofysik
Sahlgrenska Cancer Center
Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Språk en
Ämneskategorier Cancer och onkologi, Radiofysik, Strålningsbiologi

Sammanfattning

Radionuclide therapy using 177Lu-octreotate is a promising treatment option for neuroendocrine tumors with overexpression of somatostatin receptors (SSTR). In order to screen and evaluate the usefulness of 177Lu-octreotate for therapy of a specific neuroendocrine tumor type, knowledge of the binding and internalization of the 177Lu-octreotate to tumor cells is needed. The aim of this study was to determine the binding and internalization of 177Lu-octreotate in three neuroblastoma (NB) cell lines and to perform biodistribution studies in animals bearing NB. Binding and internalization of 177Lu-octreotate to the human NB cell lines IMR-32 and CLB-BAR were investigated in vitro. Cell cultures were incubated with various amounts of 177Lu-octreotate with or without excess of octreotide and harvested at 24 h and 48 h after administration. The amount of 177Lu associated to the membrane and internalized into the cells were determined. IMR-32, CLB-BAR and GEMO bearing BALB/c nude mice (n=5-6/group) were i.v. injected with 15 MBq 177Lu-octreotate and killed 1 h, 24 h and 7 days after administration. Tissue samples were collected and radioactivity concentrations were determined. Tumor-to-normal-tissue ratios (T/N) were calculated and compared with previous data. The highest binding and internalization of 177Lu in vitro occurred after 48 h: 78% and 47% of the 177Lu-octreotate in IMR-32 and CLB-BAR cells, respectively. Binding and internalization was successfully blocked with octreotide, indicating a specific uptake. In the mice bearing GEMO, T/Blood and T/Kidney values 1 h after injection were 18 and 0.71, respectively, and 7 days after injection 2300 and 27, respectively. Corresponding values for IMR-32 were 7.5 and 0.40; 1300 and 7.8, 1 h and 7 d after injection, respectively. Corresponding values for CLB-BAR were 18 and 0.24; 113 and 0.94, 1 h and 7 d after injection, respectively. This study clearly shows the potential of 177Lu-octreotate as a therapeutic alternative in the treatment of metastatic NB. The T/N values for all three tumor types investigated showed high values compared with previously investigated neuroendocrine tumor types. The results are very promising, and future studies will characterize anti-tumor effects following 177Lu-octreotate therapy.

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