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 (<i>N</i>,<i>N</i>′-bis­[2-hydroxy-5-(carboxyethyl)­benzyl]­ethylenediamine-<i>N</i>,<i>N</i>′-diacetic acid) was coupled to the bombesin peptides: HBED-C-BN(2–14) <b>1</b>, HBED-CC-PEG₂-[d-Tyr⁶,β-Ala¹¹,Thi¹³,Nle¹⁴]-BN­(6–14) <b>2</b>, HBED-CC-Y-[d-Phe⁶,Sta¹³,Leu¹⁴]-BN­(6–14) (Y = 4-amino-1-carboxymethyl­piperidine) <b>3</b>, and HBED-CC-{PEG₂-Y-[d-Phe⁶,Sta¹³,Leu¹⁴]-BN­(6–14)}₂ <b>4</b> (homodimer). Compounds <b>1</b>–<b>4</b> 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 [⁶⁸Ga]<b>1</b> and [⁶⁸Ga]<b>2</b> were mainly internalized while antagonists [⁶⁸Ga]<b>3</b> and [⁶⁸Ga]<b>4</b> 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). [⁶⁸Ga]<b>4</b> showed the highest cell-bound radioactivity (PC-3 and T47D). In vivo, tumor (PC-3) targeting for [⁶⁸Ga]<b>3</b> and [⁶⁸Ga]<b>4</b> increased over time, with dynamic μPET showing clearer tumors images at later time points. [⁶⁸Ga]<b>3</b> and [⁶⁸Ga]<b>4</b> can be considered suitable PET tracers for imaging PCa and BCa expressing GRPr