At-211 labeled substance P (5-11) as potential radiopharmaceutical for glioma treatment

作者：Lyczko Monika^*; Pruszynski Marek; Majkowska Pilip Agnieszka; Lyczko Krzysztof; Was Bogdan; Meczynska Wielgosz Sylwia; Kruszewski Marcin; Szkliniarz Katarzyna; Jastrzebski Jerzy; Stolarz Anna; Bilewicz Aleksander

来源：Nuclear Medicine and Biology, 2017, 53: 1-8.

DOI：10.1016/j.nucmedbio.2017.05.008

• Radioiodination
• Astatine-211
• Rhodium complexes
• Substance P
• Macrocyclic thioether

Introduction: The purposes of the present work were to label substance P (5-11) with At-211 using a rhodium(III) complex with a bifunctional ligand-2-(1,5,9,13-tetrathiacyclohexadecan-3-yloxy)acetic acid ([16aneS(4)]-COOH) and to assess the in vitro stability and toxicity of the obtained radiobioconjugate.
Methods: Two approaches were evaluated to obtain I-131/At-211-Rh[16aneS(4)]-SP5-11 radiobioconjugates, based on 2-step and 1-step syntheses. In the first method I-131/At-211-Rh[16aneS(4)]-COOH complexes were obtained that required further coupling to a biomolecule. In the second approach, the bioconjugate [16aneS(4)]-SP5-11 was synthesized and further labeled with I-131 and At-211 through the utilization of a Rh(III) metal cation bridge. The synthesized compounds were analyzed by HPLC, TLC and paper electrophoresis.
Results: The I-131/At-211-Rh[16aneS(4)]-COOH complexes were obtained in high yield and possessed good stability in PBS and CSF. Preliminary studies on coupling of I-131-Rh[16aneS(4)]-COOH to substance P (5-11) in 2-step synthesis showed that this procedure was too long with respect to At-211 half-life, prompting us to improve it by finally using a 1-step synthesis. This strategy not only shortened the labeling time, but also increased final yield of I-131/At-211-Rh[16aneS(4)]-SP5-11 radiobioconjugates. The stability of both compounds in PBS and CSF was high. Toxicity studies with the At-211-Rh[16aneS(4)]-SP5-11 demonstrated that radiobioconjugate significantly reduced T98G cell viability in a dose dependent manner reaching 20% of survival at the highest radioactivity 1200 kBq/mL
Conclusions: The radiobioconjugate At-211-Rh[16aneS(4)]-SP5-11 revealed its potential in killing glioma T98G cells during in vitro studies; therefore further animal studies to are required to determine its in vivo stability and treatment potential in normal and xenografted mice.

• 出版日期2017-10