Evaluation of a ⁶⁴Cu‑labeled 1,4,7‑triazacyclononane, 1‑glutaric acid‑4,7 acetic acid (NODAGA)‑galactose‑bombesin analogue as a PET imaging probe in a gastrin‑releasing peptide receptor‑expressing prostate cancer xenograft model

Int J Oncol. 2015 Mar;46(3):1159-68. doi: 10.3892/ijo.2015.2832. Epub 2015 Jan 9.


Gastrin‑releasing peptide receptor (GRPR) is overexpressed by a variety of human tumors and in particular, identified to be upregulated in prostate cancers. The current study aimed to develop clinically translatable BBN analogue‑based radioligands for positron emission tomography (PET) of GRPR‑positive tumors. We developed radiolabeled BBN analogues and modified radiolabeled galacto‑BBN analogues and then investigated their tumor‑targeting efficacy in vivo. The chelator 1,4,7‑triazacyclononane, 1‑glutaric acid‑4,7 acetic acid (NODAGA) was used to radiolabel the peptides with 64Cu. The peptides were evaluated by measuring cell‑based receptor‑binding affinities. Biodistribution experiments and small animal imaging using PET were performed in nude mice bearing subcutaneous PC3 human prostate cancer xenografts. The conjugates were radiolabeled with yields >99%. The stability assay showed that [64Cu]NODAGA‑BBN and [64Cu]NODAGA‑galacto‑BBN remained stable in both human and mouse serum for 1 h at 37˚C. PET images of PC3 tumor‑bearing nude mice were acquired at 1, 3, 24, 48 and 72 h after injection. [64Cu]NODAGA‑galacto‑BBN showed retention in tumors for 72 h, low liver uptake, and rapid renal clearance. PET imaging results were also confirmed by biodistrubution 1 and 3 h after injection. [64Cu]NODAGA‑BBN and [64Cu]NODAGA‑galacto‑BBN are promising new PET probes for GRPR‑positive prostate cancer.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates* / chemistry
  • Acetates* / pharmacokinetics
  • Animals
  • Bombesin* / analogs & derivatives
  • Bombesin* / pharmacokinetics
  • Cell Line, Tumor
  • Copper Radioisotopes* / pharmacokinetics
  • Female
  • Galactose / chemistry
  • Galactose / pharmacokinetics
  • Heterocyclic Compounds, 1-Ring* / chemistry
  • Heterocyclic Compounds, 1-Ring* / pharmacokinetics
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Positron-Emission Tomography / methods*
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Receptors, Bombesin / genetics*


  • 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
  • Acetates
  • Copper Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Receptors, Bombesin
  • Bombesin
  • Galactose