213-Bi-DOTATATE for Targeted Alpha Therapy in Neuroendocrine Tumours
213-Bi-DOTATATE voor doelgerichte alfa-therapie voor neuroendocriene tumoren
Targeted alpha therapy (TAT) is promising for improvement of current peptide receptor radionuclide therapy for patient with metastatic neuroendocrine tumours. Due to the high LET of alpha particles, the possibility to cause double strand breaks in the DNA of a tumour cell is much higher than after therapy using beta particle emitters. At the same time, healthy tissues can be spared because of the short path length of alpha particles.
213 Bismuth (213 Bi, an alpha emitter with a half-life of 46 min) was eluted from a 225 Ac/213 Bi generator. 213 Bi was attached to a peptide via a chelator, in our case a somatostatin analogue with the DOTA chelator, DOTA-Tyr3-octreotate (DOTATATE).
In this thesis, 213 Bi-DOTATATE was used for TAT to investigate whether it is superior compared to DOTATATE labelled with beta particle emitters, like 177 Lu-DOTATATE for treatment of neuroendocrine tumours with somatostatin receptor expression. The stability of 213 Bi-DOTATATE was investigated; the labelled peptide showed high stability up to 2 h after labelling. 213 Bi-DOTATATE showed higher therapeutic efficacy in vitro compared to 177 Lu-DOTATATE; a 5x more tumour cells killing potency was found. 213 Bi-DOTATATE prolonged survival in xenografted mice with different tumour models with varying somatostatin receptor density and tumour size. Potential renal toxicity could be managed by renal protectant L-lysine application. Furthermore, biodistribution was imaged by a special SPECT camera dedicated to small animals imaging.
Overall, 213 Bi-DOTATATE showed to be promising for TAT for treatment of neuroendocrine tumours with somatostatin expression.
|Keywords||Targeted alpha therapy, 213-Bismuth, Dosimetry, L-lysine|
|Promotor||M. de Jong (Marion) , W.A.P. Breeman (Woulter) , M. Konijnenberg (Mark)|
|Publisher||Erasmus University Rotterdam|
Chan, H.S. (2017, October 31). 213-Bi-DOTATATE for Targeted Alpha Therapy in Neuroendocrine Tumours. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/102457