The radiofluorination of silicon-rhodamines for bimodal PET and NIR-optical imaging [PET/OI]

Ziel/Aim The combination of non-invasive PET and optical imaging techniques for tumor identification and resection are highly in demand. This strategy is emerging to precisely differentiate between healthy and affected tumor tissues, which is of most relevance for preoperative planning (prestaging) followed by R0-tumor resection via image-guided intraoperative surgery. The goal of this work is the development of radiofluorinated near-infrared (NIR) fluorophores for PET and optical imaging. The fluorophores were prepared via multistep organic synthesis for radiolabeling with fluorine-18 with the aim to elucidate their potential as imaging probes for the detection of tumors. Moreover, the dyes were conjugated to the PSMA-1007 binding motif, as a generic prominent tumor targeting vector for enrichment in prostate tumors ([1]).

Methodik/Methods We have designed fluorophores of the silicon-rhodamine (SiR) family with optical properties in the NIR region (ca. 650 nm) ([2]). The SiRs were radiolabeled by using the strategy for copper-mediated radiofluorination of arylboronic acids ([3]). The dyes were chemically characterized and their radiolabeling properties were analyzed.

Ergebnisse/Results Novel boronic acid functionalized SiRs were obtained in overall chemical yields up to 68 %. The SiRs were conjugated to the PSMA-1007 based binding moiety to achieve selective enrichment in tumors ([1]). The dyes show high extinction coefficients up to 72.000 M^-1cm^-1, quantum yields of 0.33 and high photostabilities making them useful for NIR-optical imaging. The radiofluorinated SiRs show high human serum stabilities and molar activities of 70 GBq/µmol with promising properties for in-vitro/in-vivo experiments.

Schlussfolgerungen/Conclusions Multiple NIR fluorophores based on the SiR lead structure have been synthesized and their accessibility for radiolabeling was evaluated. Ideal optical- and radiolabeling properties show promising features for further biological performance. Currently, our first-in-class radiolabeled and bioconjugated SiRs are subject to biological evaluation.

• Literatur/References

• 1 K. Kopka. et al., J. Nucl. Med. 2015; 56 , 914-920.
• 2 T. Nagano. et al., J. Am. Chem. Soc. 2012; 134 , 5029-5031.
• 3 B. Neumaier. et al., Chem. Eur. J. 2017; 23 , 3251-3556.

Publication History

Article published online:
08 April 2021