Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?

Eur J Nucl Med Mol Imaging. 2007 Jul;34(7):982-93. doi: 10.1007/s00259-006-0317-x. Epub 2007 Jan 16.

Abstract

Purpose: Gallium-68 is a metallic positron emitter with a half-life of 68 min that is ideal for the in vivo use of small molecules, such as [68Ga-DOTA,Tyr3]octreotide, in the diagnostic imaging of somatostatin receptor-positive tumours. In preclinical studies it has shown a striking superiority over its 111In-labelled congener. The purpose of this study was to evaluate whether third-generation somatostatin-based, radiogallium-labelled peptides show the same superiority.

Methods: Peptides were synthesised on solid phase. The receptor affinity was determined by in vitro receptor autoradiography. The internalisation rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J.

Results: All peptides showed high affinities on hsst2, with the highest affinity for the Ga(III)-complexed peptides. On hsst3 the situation was reversed, with a trend towards lower affinity of the Ga(III) peptides. A significantly increased internalisation rate was found in sst2-expressing cells for all 67Ga-labelled peptides. Internalisation into HEK-sst3 was usually faster for the 111In-labelled peptides. No internalisation was found into sst5. Biodistribution studies employing [67Ga-DOTA,1-Nal3]octreotide in comparison to [111In-DOTA,1-Nal3]octreotide and [67Ga-DOTA,Tyr3]octreotide showed a significantly higher and receptor-mediated uptake of the two 67Ga-labelled peptides in the tumour and somatostatin receptor-positive tissues. A patient study illustrated the potential advantage of a broad receptor subtype profile radiopeptide over a high-affinity sst2-selective radiopeptide.

Conclusion: This study demonstrates that 67/68Ga-DOTA-octapeptides show distinctly better preclinical, pharmacological performances than the 111In-labelled peptides, especially on sst2-expressing cells and the corresponding animal models. They may be excellent candidates for further development for clinical studies.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Gallium Radioisotopes / chemistry
  • Gallium Radioisotopes / pharmacokinetics*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics*
  • Isotope Labeling / methods
  • Male
  • Metabolic Clearance Rate
  • Organ Specificity
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / metabolism*
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / chemistry
  • Rats
  • Rats, Inbred Lew
  • Sensitivity and Specificity
  • Somatostatin / chemistry
  • Somatostatin / pharmacokinetics*
  • Tissue Distribution

Substances

  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Radiopharmaceuticals
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Somatostatin