GRPR-selective PET imaging of prostate cancer using [18F]-lanthionine-bombesin analogs

The gastrin-releasing peptide receptor (GRPR) is overexpressed in a variety of human malignancies, including prostate cancer. Bombesin (BBN) is a 14 amino acids peptide that selectively binds to GRPR. In this study, we developed two novel Al18F-labeled lanthionine-stabilized BBN analogs, designated Al18F-NOTA-4,7-lanthionine-BBN and Al18F-NOTA-2,6-lanthionine-BBN, for positron emission tomography (PET) imaging of GRPR expression using xenograft prostate cancer models. (Methyl)lanthionine-stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN analogs were conjugated with a NOTA chelator and radiolabeled with Al18F using the aluminum fluoride strategy. Al18F-NOTA-4,7-lanthionine-BBN and Al18F-NOTA-2,6-lanthionine-BBN was labeled with Al18F with good radiochemical yield and specific activity > 30 GBq/μmol for both radiotracers. The log D values measured for Al18F-NOTA-4,7-lanthionine-BBN and Al18F-NOTA-2,6-lanthionine-BBN were −2.14 ± 0.14 and −2.34 ± 0.15, respectively. In athymic nude PC-3 xenografts, at 120 min post injection (p.i.), the uptake of Al18F-NOTA-4,7-lanthionine-BBN and Al18F-NOTA-2,6-lanthionine-BBN in prostate cancer (PC-3) mouse models was 0.82 ± 0.23% ID/g and 1.40 ± 0.81% ID/g, respectively. An excess of unlabeled ɛ-aminocaproic acid-BBN(7-14) (300-fold) was co-injected to assess GRPR binding specificity. Tumor uptake of Al18F-NOTA-4,7-lanthionine-BBN and Al18F-NOTA-2,6-lanthionine-BBN in PC-3 tumors was evaluated by microPET (μPET) imaging at 30, 60 and 120 min p.i. Blocking studies showed decreased uptake in PC-3 bearing mice. Stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN peptides were rapidly and successfully labeled with 18F. Both tracers may have potential for GRPR-positive tumor imaging.