PET-Based Human Dosimetry of the Dimeric αvβ3 Integrin Ligand 68Ga-DOTA-E-[c(RGDfK)]2, a Potential Tracer for Imaging Tumor Angiogenesis

J Nucl Med. 2016 Mar;57(3):404-9. doi: 10.2967/jnumed.115.161653. Epub 2015 Nov 19.

Abstract

Peptides containing the Arg-Gly-Asp (RGD) sequence have high affinity for αvβ3 integrin receptors overexpressed in tumor cells. The objective of this research was to determine the biodistribution and estimate the radiation dose from (68)Ga-DOTA-E-[c(RGDfK)]2 using whole-body PET scans in humans.

Methods: Five healthy volunteers (2 women, 3 men; mean age ± SD, 37.2 ± 15.6 y; range, 28-65 y; mean weight, 79.2 ± 21.0 kg; range, 64-115 kg) were included. After intravenous injection of the tracer (198.3 ± 3.3 MBq), 3 successive whole-body (vertex to mid thigh) PET/CT scans at 3 time points (30, 60, and 120 min) were obtained on a 16-slice PET/CT scanner. The subjects did not void the bladder until the entire series of images was completed. Low-dose CT without contrast agent was used for anatomic localization and attenuation correction. OLINDA/EXM software was applied to calculate human radiation doses using the reference adult model.

Results: The highest uptake was in the urinary bladder, followed by the liver, kidneys, and spleen, in descending order. The critical organ was the urinary bladder wall. The mean effective doses (all subjects, men and women) were 34.1 ± 4.9, 31.0 ± 2.4, and 20.9 ± 5.2 μSv/MBq for the no-voiding, 2.5-h-voiding, and 1-h-voiding models, respectively.

Conclusion: Of particular interest in this research was the visualization of the choroid plexus and ventricular system, which seems to be a characteristic of RGD-dimeric peptides. Measured absorbed doses and effective doses are comparable to other previously reported RGD-based radiopharmaceuticals labeled with (68)Ga and (18)F. Therefore, (68)Ga-DOTA-E-[c(RGDfK)]2 can safely be used for imaging integrin αVβ3 expression.

Keywords: 68Ga-DOTA-E-[c(RGDfK)]2; RGD–dimeric peptides; angiogenesis; human dosimetry; αVβ3 integrin receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Coordination Complexes / pharmacokinetics*
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Integrin alphaVbeta3 / biosynthesis
  • Integrin alphaVbeta3 / metabolism*
  • Ligands
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms / diagnostic imaging*
  • Neovascularization, Pathologic / diagnostic imaging*
  • Peptides, Cyclic / pharmacokinetics*
  • Positron-Emission Tomography
  • Radiometry
  • Radiopharmaceuticals* / pharmacokinetics
  • Tissue Distribution

Substances

  • 68Ga-DOTA-E-(c(RGDfK))2
  • Coordination Complexes
  • Integrin alphaVbeta3
  • Ligands
  • Peptides, Cyclic
  • Radiopharmaceuticals