Integrin αvβ3 as a Promising Target to Image Neoangiogenesis Using In-House Generator-Produced Positron Emitter (68)Ga-Labeled DOTA-Arginine-Glycine-Aspartic Acid (RGD) Ligand

Cancer Biother Radiopharm. 2015 Jun;30(5):217-24. doi: 10.1089/cbr.2014.1781.

Abstract

For the growth and spread of a tumor beyond 2 mm, angiogenesis plays a crucial role, and association of various integrins with angiogenesis is evidential. The aim of the study was radiolabeling of DOTA-chelated RGD (arginine-glycine-aspartic acid) peptide with (68)Ga for PET imaging in locally advanced breast carcinoma. DOTA-RGD was incubated with (68)GaCl3, eluted in 0.05 m HCl. Elution volume, peptide amount, and reaction pH were studied. Radio-ITLC, gas chromatography, endotoxin, and sterility testing were performed. Serial (n=3) and whole-body (n=2) PET/CT imaging was done on patients post i.v. injection of 111-185 MBq of (68)Ga-DOTA-RGD. Maximum radiolabeling yield was achieved with 3 mL elution volume of 15-20 μg peptide at pH 3.5-4.0 with 10 minutes of incubation at 95°C. Product samples were sterile having 99.5% radiochemical purity with residual ethanol content and endotoxins in injectable limits. Intense radiotracer uptake was noticed in the tumor with SUVmax 15.3 at 45 minutes in serial images. Physiological radiotracer uptake was seen in the liver, spleen, ventricles, and thyroid with excretion through the kidneys. The authors concluded that (68)Ga-DOTA-RGD has the potential for imaging α,vβ3 integrin-expressing tumors.

Keywords: 68Ga; PET/CT imaging; RGD; angiogenesis; αvβ3 integrin.

MeSH terms

  • Adult
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / diagnostic imaging*
  • Female
  • Gallium Radioisotopes*
  • Heterocyclic Compounds, 1-Ring / chemical synthesis*
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics
  • Humans
  • Integrin alphaVbeta3 / analysis*
  • Middle Aged
  • Multimodal Imaging
  • Neovascularization, Pathologic / diagnostic imaging*
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacokinetics
  • Positron-Emission Tomography
  • Quality Control
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Tomography, X-Ray Computed
  • Whole Body Imaging

Substances

  • 68Ga-DOTA-Arg-Gly-Asp
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Integrin alphaVbeta3
  • Oligopeptides
  • Radiopharmaceuticals