Heterobivalent peptidic
ligands (HBPLs), designed to address two different receptors independently, are highly promising
tumor imaging agents. For example,
breast cancer has been shown to concomitantly and complementarily overexpress the
neuropeptide Y receptor subtype 1 (NPY(Y₁)R) as well as the
gastrin-releasing peptide receptor (GRPR). Thus, radiolabeled HBPLs being able to bind these two receptors should exhibit an improved
tumor targeting efficiency compared to monospecific
ligands. We developed here such bispecific HBPLs and radiolabeled them with 68Ga, achieving high radiochemical yields, purities, and molar activities. We evaluated the HBPLs and their monospecific reference
peptides in vitro regarding stability and uptake into different
breast cancer cell lines and found that the 68Ga-HBPLs were efficiently taken up via the GRPR. We also performed in vivo PET/CT imaging and ex vivo biodistribution studies in T-47D
tumor-bearing mice for the most promising 68Ga-HBPL and compared the results to those obtained for its scrambled analogs. The
tumors could easily be visualized by the newly developed 68Ga-HBPL and considerably higher
tumor uptakes and
tumor-to-background ratios were obtained compared to the scrambled analogs in and ex vivo. These results demonstrate the general feasibility of the approach to use bispecific radioligands for in vivo imaging of
breast cancer.