Fluorine-18 Labelling of Neurotensin Analogues for the Development of Tumour Imaging Agents

A promising approach for tracking tumours is to use radiolabelled derivatives of peptides such as Neurotensin (NT). This neuropeptide exhibits a high specific affinity to receptors located on various tumours like small cell lung carcinoma or human colon carcinoma. In order to develop a radiotracer to image the neurotensin receptor with PET the hexapeptide NT(8-13) and derivatives, such as pseudopeptides [Arg⁸psi(CH₂NH)Arg⁹]NT(8-13) and [NMe-Arg⁸]NT(8-13) may serve as valuable starting materials.
Our labelling experiments revealed that [¹⁸F]SFB reacts with N-terminal Arg-peptides like NT(8-13) or the metabolically stabilized pseudopeptide [Arg⁸psi(CH₂NH)Arg⁹]NT(8-13) with reasonable to good chemoselectivities in aqueous buffered solutions at pH values between 7.2 and 8.3. The radioactive product was identified by chromatographic comparison with a reference compound. The reactions carried out with nonradioactive SFB were shown to give the corresponding 4-FB peptides of which their structural identity was confirmed by proton NMR and MS studies. In summary the desired products of the reaction of [¹⁸F]SFB with NT(8-13) as well as [Arg⁸psi(CH₂NH)Arg⁹]NT(8-13) were obtained after HPLC purification with r.c.y. of up to 43 % (related to [¹⁸F]SFB; decay corrected) within 80 min.