A Comparison of High- Versus Low-Linear Energy Transfer Somatostatin Receptor Targeted Radionuclide Therapy In Vitro

Abstract

Introduction: The somatostatin analog [DOTA⁰-Tyr³]-octreotide (DOTATOC) has been widely used to target somatostatin receptor expressing tumors for therapy using radionuclides such as ⁹⁰Y or ¹⁷⁷Lu.

Aim: This aim of this study was to compare the effects of DOTATOC labeled to high linear energy transfer (LET) α-emitter ²¹³Bi and low-LET β-emitter ¹⁷⁷Lu

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 α-emitter ²¹³Bi and low-LET β-emitter ¹⁷⁷Lu were investigated using cell survival assay. The apoptotic effects were investigated using Cell Death Detection ELISA^PLUS10×. The cumulated activity and the mean absorbed dose per unit cumulated activity were calculated using MIRD cellular Svalues.

Results: ²¹³Bi-DOTATOC had an approximately four times greater induction of apoptosis than ¹⁷⁷Lu-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: ²¹³Bi-DOTATOC is significantly more potent than ¹⁷⁷Lu-DOTATOC

in vitro because of its high-LET α-emission.²¹³Bi-DOTATOC shows enhanced effects on mitotic and apoptotic cell deaths.