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

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 Al(18)F-labeled lanthionine-stabilized BBN analogs, designated Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-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 Al(18)F using the aluminum fluoride strategy. Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN was labeled with Al(18)F with good radiochemical yield and specific activity>30 GBq/μmol for both radiotracers. The logD values measured for Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-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 Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-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 Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-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 (18)F. Both tracers may have potential for GRPR-positive tumor imaging.

• Authors: G Carlucci, A Kuipers, H J K Ananias, D de Paula Faria, R A J O Dierckx, W Helfrich, R Rink, G N Moll, I J de Jong, P H Elsinga
• Journal: Peptides (Peptides) Vol. 67 Pg. 45-54 (May 2015) ISSN: 1873-5169 [Electronic] United States
• PMID: 25797109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Fluorine Radioisotopes
• Radiopharmaceuticals
• Receptors, Bombesin
• Sulfides
• lanthionine
• Alanine
• Bombesin

Topics

• Alanine (analogs & derivatives, pharmacokinetics)
• Animals
• Bombesin (pharmacokinetics)
• Cell Line, Tumor
• Fluorine Radioisotopes (pharmacokinetics)
• Humans
• Male
• Mice, Nude
• Neoplasm Transplantation
• Positron-Emission Tomography
• Prostatic Neoplasms (diagnostic imaging, metabolism)
• Radiopharmaceuticals (pharmacokinetics)
• Receptors, Bombesin (metabolism)
• Sulfides (pharmacokinetics)
• Tissue Distribution
• X-Ray Microtomography