New PET imaging agents could enable earlier detection of hard-to-treat cancers
Researchers have developed two radioactive imaging agents that can detect gastrin-releasing peptide receptors, markers present in several aggressive cancers including prostate and breast tumors. The agents cleared quickly from the bloodstream while accumulating strongly in tumors, suggesting they could improve early diagnosis and enable better patient stratification for precision therapies.
Originaltitel: Exploring the theranostic potential of two metabolically stable GRPR-targeting peptides labelled with Ga-68 for PET imaging
Abstract Background Gastrin-releasing peptide receptor (GRPR) attracts increasing attention as a target for radiotheranostic applications. We previously developed a metabolically stable GRPR-targeting peptide, incorporating α-methyl-L-tryptophan within its sequence (PEG 2 -Pip-D-Phe 6 -Gln 7 -MetTrp 8 -Ala 9 -Val 10 -Sar 11 -His 12 -Sta 13 -Leu 14 -NH 2 ) and coupled it to DOTAGA chelator (PKB2) and to DOTA (PKB3). When labelled with Lu-177, both peptide variants demonstrated promising properties for targeted radionuclide therapy. Results In this study, we aimed to evaluate the diagnostic counterparts of PKB2 and PKB3 by radiolabelling them with Ga-68 for positron emission tomography (PET) imaging. [ 68 Ga]Ga-PKB2 and [ 68 Ga]Ga-PKB3 were produced with radiochemical yields over 99% and radiochemical purities over 97%. Both radiopeptides showed a high GRPR affinity with IC 50 values in the low nanomolar range and a GRPR-mediated uptake in PC-3 cells with slow internalization. The labelled peptides [ 68 Ga]Ga-PKB2 and [ 68 Ga]Ga-PKB3 demonstrated fast clearance with activity concentration in blood below 0.5%IA/g at 2 pi, and a high tumour activity uptake in PC-3 xenografts (16 ± 3%IA/g and 17 ± 2%IA/g, respectively). [ 68 Ga]Ga-PKB3 had a significantly higher activity uptake in the pancreas (GRPR-expressing organ) and lower uptake in the kidneys than [ 68 Ga]Ga-PKB2. PET/CT images were concordant with the biodistribution results, clearly delineating tumour tissue. Conclusions [ 68 Ga]Ga-PKB2 and [ 68 Ga]Ga-PKB3 are promising PET tracers for imaging of GRPR-positive tumours and are potential diagnostic counterparts to their 177 Lu-labelled analogues, supporting their use as a 177 Lu/ 68 Ga theranostic pair.