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

INTRODUCTION: The purposes of the present work were to label substance P (5-11) with 211 At using a rhodium(III) complex with a bifunctional ligand-2-(1,5,9,13-tetrathiacyclohexadecan-3-yloxy)acetic acid ([16aneS4 ]-COOH) and to assess the in vitro stability and toxicity of the obtained radiobioconjugate.

METHODS: Two approaches were evaluated to obtain 131 I/211 At-Rh[16aneS4 ]-SP5-11 radiobioconjugates, based on 2-step and 1-step syntheses. In the first method 131 I/211 At-Rh[16aneS4 ]-COOH complexes were obtained that required further coupling to a biomolecule. In the second approach, the bioconjugate [16aneS4 ]-SP5-11 was synthesized and further labeled with 131 I and 211 At through the utilization of a Rh(III) metal cation bridge. The synthesized compounds were analyzed by HPLC, TLC and paper electrophoresis.

RESULTS: The 131 I/211 At-Rh[16aneS4 ]-COOH complexes were obtained in high yield and possessed good stability in PBS and CSF. Preliminary studies on coupling of 131 I-Rh[16aneS4 ]-COOH to substance P (5-11) in 2-step synthesis showed that this procedure was too long with respect to 211 At 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 131 I/211 At-Rh[16aneS4 ]-SP5-11 radiobioconjugates. The stability of both compounds in PBS and CSF was high. Toxicity studies with the 211 At-Rh[16aneS4 ]-SP5-11 demonstrated that radiobioconjugate significantly reduced T98G cell viability in a dose dependent manner reaching 20% of survival at the highest radioactivity 1200kBq/mL.

CONCLUSIONS: The radiobioconjugate 211 At-Rh[16aneS4 ]-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.