GRPR-selective PET imaging of prostate cancer using [F-18]-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 (AlF)-F-18-labeled lanthionine-stabilized BBN analogs, designated Al(18)FNOTA-4,7-lanthionine-BBN and Al-18F-NOTA-2,6-lanthionine-BBN, for positron emission tomography (PET) imaging of GRPR expression using xenograft prostate cancer models. (Methyl)lanthioninestabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN analogs were conjugated with a NOTA chelator and radiolabeled with (AlF)-F-18 using the aluminum fluoride strategy. (AlF)-F-18-NOTA-4,7-lanthionine-BBN and (AlF)-F-18-NOTA-2,6-lanthionine-BBN was labeled with (AlF)-F-18 with good radiochemical yield and specific activity >30 GBq/p,mol for both radiotracers. The log D values measured for (AlF)-F-18-NOTA-4,7-lanthionineBBN and (AlF)-F-18-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 (AlF)-F-18-NOTA-4,7-lanthionine-BBN and (AlF)-F-18-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 e-aminocaproic acid-BBN(7-14) (300-fold) was co-injected to assess GRPR binding specificity. Tumor uptake of (AlF)-F-18-NOTA-4,7-lanthionine-BBN and (AlF)-F-18-NOTA-2,6-lanthionine-BBN in PC-3 tumors was evaluated by microPET ( p,PET) imaging at 30,60 and 120 min p.i. Blocking studies showed decreased uptake in PC-3 bearing mice. Stabilized 4,7-lanthionineBBN and 2,6-lanthionine-BBN peptides were rapidly and successfully labeled with F-18. Both tracers may have potential for GRPR-positive tumor imaging. (C) 2015 Elsevier Inc. All rights reserved.