Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer

Bioconjug Chem. 2016 Aug 17;27(8):1857-64. doi: 10.1021/acs.bioconjchem.6b00279. Epub 2016 Jul 26.

Abstract

Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high contrast, and optimal pharmacokinetics is still very challenging. Herein, a novel bombesin (BBN) analogue (named SCH1) based on JMV594 peptide modified with an 8-amino octanoic acid spacer (AOC) was thus designed and conjugated with the metal chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). The resulting NODAGA-SCH1 was then radiolabeled with (68)Ga and evaluated for PET imaging of PCa. Compared with (68)Ga-NODAGA-JMV594 probe, (68)Ga-NODAGA-SCH1 exhibited excellent PET/CT imaging properties on PC-3 tumor-bearing nude mice, such as high tumor uptake (5.80 ± 0.42 vs 3.78 ± 0.28%ID/g, 2 h) and high tumor/muscle contrast (16.6 ± 1.50 vs 8.42 ± 0.61%ID/g, 2 h). Importantly, biodistribution data indicated a relatively similar accumulation of (68)Ga-NODAGA-SCH1 was observed in the liver (4.21 ± 0.42%ID/g) and kidney (3.41 ± 0.46%ID/g) suggesting that the clearance is through both the kidney and the liver. Overall, (68)Ga-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetates / chemistry
  • Acetates / metabolism*
  • Acetates / pharmacokinetics
  • Animals
  • Biological Transport
  • Cell Line, Tumor
  • Drug Stability
  • Gallium Radioisotopes*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / metabolism*
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics
  • Humans
  • Male
  • Mice
  • Octanols / chemistry
  • Positron Emission Tomography Computed Tomography / methods*
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / pathology
  • Receptors, Bombesin / metabolism*
  • Tissue Distribution
  • Water / chemistry

Substances

  • 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
  • Acetates
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Octanols
  • Receptors, Bombesin
  • Water