Monomeric and Dimeric ⁶⁸Ga-Labeled Bombesin Analogues for Positron Emission Tomography (PET) Imaging of Tumors Expressing Gastrin-Releasing Peptide Receptors (GRPrs)

The GRPr, highly expressed in prostate PCa and breast cancer BCa, is a promising target for the development of new PET radiotracers. The chelator HBED-CC ( N, N ′-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine- N, N ′-diacetic acid) was coupled to the bombesin peptides: HBED-C-BN(2–14) 1, HBED-CC-PEG 2 -[ d -Tyr 6,β-Ala 11,Thi 13,Nle 14 ]-BN(6–14) 2, HBED-CC-Y-[ d -Phe 6,Sta 13,Leu 14 ]-BN(6–14) (Y = 4-amino-1-carboxymethylpiperidine) 3, and HBED-CC-{PEG 2 -Y-[ d -Phe 6,Sta 13,Leu 14 ]-BN(6–14)} 2 4 (homodimer). Compounds 1 – 4 presented high binding affinities for GRPr (T47D, 0.56–3.51 nM; PC-3, 2.12–4.68 nM). In PC-3 and T47D cells, agonists [ 68 Ga] 1 and [ 68 Ga] 2 were mainly internalized while antagonists [ 68 Ga] 3 and [ 68 Ga] 4 were surface bound. Cell-related radioactivity reached a maximum after 45 min, while tracer levels followed GRPr expression (PC-3 > T47D > LNCaP > MDA-MB-231). [ 68 Ga] 4 showed the highest cell-bound radioactivity (PC-3 and T47D). In vivo, tumor (PC-3) targeting for [ 68 Ga] 3 and [ 68 Ga] 4 increased over time, with dynamic μPET showing clearer tumors images at later time points. [ 68 Ga] 3 and [ 68 Ga] 4 can be considered suitable PET tracers for imaging PCa and BCa expressing GRPr.