Peptide Receptor Radionuclide Therapy In Vitro Using [111In-DTPA0]Octreotide

Journal of Nuclear Medicine

Bert F. Bernard¹  Eric P. Krenning¹  Astrid Capello¹  Wout A.P. Breeman¹  Marion de Jong¹ 

[1] Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

关键词: [¹¹¹In-diethylenetriaminepentaacetic acid(0)]octreotide;    Auger electrons;    peptide receptor radionuclide therapy;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Peptide receptor radionuclide therapy (PRRT) using [111In-DTPA0]octreotide (where DTPA is diethylenetriaminepentaacetic acid) is feasible because, besides γ-radiation, 111In emits both therapeutic Auger and internal conversion electrons having a tissue penetration of 0.02–10 and 200–500 μm, respectively. The aim of this study was to investigate the therapeutic effects of [111In-DTPA0]octreotide in a single-cell model including the effects of incubation time, radiation dose, and specific activity of [111In-DTPA0]octreotide. Finally, we discriminated between the effects of the Auger electrons and internal conversion electrons in PRRT. Methods: An in vitro, colony-forming assay to study cell survival after PRRT using the sst subtype 2–positive rat pancreatic tumor cell line CA20948 was developed. Results: In this in vitro system [111In-DTPA0]octreotide can control tumor growth to 0% survival, and the effects were dependent on incubation time, radiation dose, and specific activity used. Similar concentrations of 111In-DTPA, which is not internalized into sst-positive tumor cells like [111In-DTPA0]octreotide, did not influence tumor survival. Excess unlabeled octreotide (10−6 mol/L) could decrease tumor cell survival to 60% of control; the addition of radiolabeled peptide ([111In-DTPA0]octreotide [10−9 mol/L] + 10−6 mol/L octreotide) did not further decrease survival. Conclusion: These in vitro studies show that the therapeutic effect of 111In is dependent on internalization, enabling the Auger electrons with their very short particle range to reach the nucleus. Our results also indicate that the PRRT effects were receptor mediated.

【 授权许可】

Unknown