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

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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)

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 (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.

Original languageEnglish
Pages (from-to)45-54
Number of pages10
JournalPeptides
Volume67
DOIs
Publication statusPublished - May-2015

Keywords

  • GRPR
  • Bombesin
  • (AlF)-F-18
  • PC-3
  • PET
  • Stability
  • GASTRIN-RELEASING-PEPTIDE
  • BOMBESIN-LIKE PEPTIDES
  • LANTIBIOTIC NISIN
  • RECEPTOR
  • TUMOR
  • ANGIOTENSIN-(1-7)
  • VISUALIZATION
  • CYCLIZATION
  • ANTAGONIST
  • (ALF)-F-18

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