In Vivo Evaluation of a Bombesin Analogue Labeled with Ga-68 and Co-55/57

Mol Imaging Biol. 2016 Jun;18(3):368-76. doi: 10.1007/s11307-015-0911-z.

Abstract

Purpose: The purpose of this study was to apply an analogue of bombesin, NOTA-AMBA, labeled with Co-55 or Ga-68, for preclinical imaging of prostate cancer.

Procedures: The peptide NOTA-AMBA was labeled with Ga-68 or Co-55 by microwave irradiation. Biodistribution in xenograft mice (PC3) was performed at 1, 4, and 24 h (only cobalt at 24 h) using a fixed amount of peptide. Four weeks post-inoculation, xenograft mice were positron emission tomography/X-ray computed tomography scanned after tail vein injection of [(68)Ga]NOTA-AMBA or [(55)Co]NOTA-AMBA.

Results: Labeling with Ga-68 and Co-55/57 was achieved in yields greater than 90 %. A radiochemical purity (RCP) of 95 and 90 % were obtained for Ga-68 and Co-55, respectively. Both radiopeptides showed high uptake in the intestines, stomach, pancreas, and in the tumor ([(68)Ga]NOTA-AMBA, 10.3 %ID/g at 1 h to 6.4 %ID/g at 4 h; [(57)Co]NOTA-AMBA, 8.2 %ID/g at 1 h to 5.3%ID/g at 24 h). Normal tissue cleared over time improving tumor-to-background ratios.

Conclusions: NOTA-AMBA was labeled in high yields and RCP with Ga-68 and Co-55/57. High tumor uptake in a subcutaneous mouse prostate cancer model was observed. At 24 h, [(55/57)Co]NOTA-AMBA showed better tumor-to-organ ratios than [(68)Ga]NOTA-AMBA at both 1 and 4 h post-injection. Hence, for imaging, [(55)Co]NOTA-AMBA was found to be superior compared to [(68)Ga]NOTA-AMBA.

Keywords: AMBA; Bombesin; Cobalt-55; Gallium-68; PET; Positron emission tomography; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Bombesin / analogs & derivatives*
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Cobalt Radioisotopes / chemistry*
  • Gallium Radioisotopes / chemistry*
  • Humans
  • Inhibitory Concentration 50
  • Male
  • Mice, SCID
  • Peptides / blood
  • Peptides / chemistry
  • Positron-Emission Tomography
  • Protein Stability
  • Radiopharmaceuticals / chemistry*
  • Tissue Distribution
  • Tomography, X-Ray Computed
  • Xenograft Model Antitumor Assays

Substances

  • Cobalt Radioisotopes
  • Gallium Radioisotopes
  • Peptides
  • Radiopharmaceuticals
  • Bombesin