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A comparison of high- versus low-linear energy transfer somatostatin receptor targeted radionuclide therapy in vitro
Tapan Nayak1, Jeffrey Norenberg, Tamara Anderson
1Radiopharmaceutical Sciences Program, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131-0001, USA.
Introduction:
The somatostatin analog [DOTA(0)-Tyr(3)]-octreotide (DOTATOC) has been widely used to target somatostatin receptor expressing tumors for therapy using radionuclides such as (90)Y or (177)Lu.
Aim:
This aim of this study was to compare the effects of DOTATOC labeled to high linear energy transfer (LET) alpha-emitter (213)Bi and low-LET beta-emitter (177)Lu in vitro.
Materials And Methods:
Somatostatin receptor (sstr)-positive cell line Capan-2 and sstr-negative control cell line A549 were used for the experiments. The effects of two exposure times using different radiation doses of high-LET alpha-emitter (213)Bi and low-LET beta-emitter (177)Lu were investigated using cell survival assay. The apoptotic effects were investigated using Cell Death Detection ELISA(PLUS)10x. The cumulated activity and the mean absorbed dose per unit cumulated activity were calculated using MIRD cellular Svalues.
Results:
(213)Bi-DOTATOC had an approximately four times greater induction of apoptosis than (177)Lu-DOTATOC and a 100 times greater induction of apoptosis than nonradiolabeled DOTATOC. Nonspecific radiolabeled tetra-azacyclododecanetetra-acetic acid (DOTA) had a less pronounced effect on the cell survival and apoptosis, as compared to the sstr-specific radiolabeled DOTATOC.
Conclusion:
(213)Bi-DOTATOC is significantly more potent than (177)Lu-DOTATOC in vitro because of its high-LET alpha-emission.(213)Bi-DOTATOC shows enhanced effects on mitotic and apoptotic cell deaths.
