Abstract
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>30GBq/μmol for both radiotracers. The logD 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 120min 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 120min 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.
Published Version
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