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Göteborgs universitets publikationer

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

Författare och institution:
Arman Romiani (Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för radiofysik); Johan Spetz (Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för radiofysik & Sahlgrenska Cancer Center); Emil Schüler (Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för radiofysik & Sahlgrenska Cancer Center); Wan Haiying (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Ruth H. Palmer (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Bengt Hallberg (Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi); Eva Forssell-Aronsson (Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för radiofysik & Sahlgrenska Cancer Center)
Publicerad i:
62nd Annual International Meeting Radiation Research Society, Waikoloa, HI, USA, October 16-19, 2016,
Publikationstyp:
Konferensbidrag - refereegranskat abstract
Publiceringsår:
2016
Språk:
engelska
Sammanfattning (abstract):
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Cancer och onkologi
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Radiologi och bildbehandling ->
Radiofysik
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Radiologi och bildbehandling ->
Strålningsbiologi
Postens nummer:
238953
Posten skapad:
2016-07-05 12:45
Posten ändrad:
2016-09-21 10:59

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