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Nordeman P, Jayendra ZP, Briard E, Li SC, Larhed M, Antoni G, Estrada S, Selvaraju RK, Åberg O, Jensen MR, Stålberg P, Skogseid B, Monazzam A
Eur J Pharm Sci 157 (-) 105647 [2021-02-01; online 2020-11-20]
With the ambition of improving the management of pancreatic neuroendocrine tumors (P-NETs), we developed and preliminary validated a novel fluorine-18 labelled HSP90 ligand. A precursor containing methoxymethyl ethers protecting groups and a tosyl as leaving group was synthesized. The target compound was labeled with nucleophilic 18F-fluoride and the protecting groups was subsequently removed with hydrochloric acid before purification. In vitro cell- and frozen section autoradiography and in vivo animal studies were performed. The precursor was successfully synthesized and utilized in the 18F-radiolabeling giving 0.5-1.0 GBq of pure product with a synthesis time of 70 min. In vitro experiments indicated a high specific binding, but in vivo studies showed no tumor uptake due to fast hepatobiliary metabolism and excretion. Despite the unfavorable in vivo properties of the tracer, the promising results from in vitro autoradiography experiments in frozen sections of P-NETs from surgical resection encourage us to continue the project aiming the improvement of in vivo properties of the tracer.
PubMed 33221456
DOI 10.1016/j.ejps.2020.105647
Crossref 10.1016/j.ejps.2020.105647
pii: S0928-0987(20)30435-8