Chelator boosted tumor-retention and pharmacokinetic properties: development of Cu labeled radiopharmaceuticals targeting neurotensin receptor.

Purpose: Accumulating evidence suggests that neurotensin (NTS) and neurotensin receptors (NTSRs) play key roles in lung cancer progression by triggering multiple oncogenic signaling pathways. This study aims to develop Cu-labeled neurotensin receptor 1 (NTSR1)-targeting agents with the potential for both imaging and therapeutic applications.

Method: A series of neurotensin receptor antagonists (NRAs) with variable propylamine (PA) linker length and different chelators were synthesized, including [Cu]Cu-CB-TE2A-iPA-NRA ([Cu]Cu-4a-c, i = 1, 2, 3), [Cu]Cu-NOTA-2PA-NRA ([Cu]Cu-4d), [Cu]Cu-DOTA-2PA-NRA ([Cu]Cu-4e, also known as [Cu]Cu-3BP-227), and [Cu]Cu-DOTA-VS-2PA-NRA ([Cu]Cu-4f).

Radiolabeling Diaminosarcophagine with Cyclotron-Produced Cobalt-55 and [Co]Co-NT-Sarcage as a Proof of Concept in a Murine Xenograft Model.

Cobalt-sarcophagine complexes exhibit high kinetic inertness under various stringent conditions, but there is limited literature on radiolabeling and in vivo positron emission tomography (PET) imaging using no carrier added Co. To fill this gap, this study first investigates the radiolabeling of DiAmSar (DSar) with Co, followed by stability evaluation in human serum and EDTA, pharmacokinetics in mice, and a direct comparison with [Co]CoCl to assess differences in pharmacokinetics. Furthermore, the radiolabeling process was successfully used to generate the NTSR1-targeted PET agent [Co]Co-NT-Sarcage (a DSar-functionalized SR142948 derivative) and administered to HT29 tumor xenografted mice.