Novel bifunctional DATA chelator for quick access to site-directed PET 68Ga-radiotracers: preclinical proof-of-principle with [Tyr3]octreotide

Dalton Trans. 2017 Oct 31;46(42):14584-14590. doi: 10.1039/c7dt01684k.

Abstract

Molecular imaging of tumors with the PET radionuclide 68Ga has gained momentum in clinical oncology due to the expanding availability of commercial 68Ge/68Ga-generators in combination with state-of-the-art PET/CT and PET/MRI hybrid imaging systems. Concurrently, interesting peptide-based or small-size vectors have been developed for theranostic use in cancer patients. Owing to the short half-life of 68Ga (t1/2 = 67.7 min) and the sensitivity of many targeting biomolecules, labeling and kit reconstitution in mild conditions allowing for quick access to ready-for-injection PET-tracers are highly desirable. The novel DATA ((6-pentanoic acid)-6-(amino)methy-1,4-diazepinetriacetate) chelator previously showing promising qualities for kit type labeling, was coupled to TOC ([Tyr3]octreotide). We herein report results from a first proof-of-principle study directly comparing 67Ga-DATA-TOC with the well-established 67Ga-DOTA-TOC in a series of preclinical models. Both analogs were shown to be sst2-preferring and specifically internalized in AR42J and HEK293-hsst2 cells, with 67Ga-DOTA-TOC internalizing faster in both cell lines. Similarly, after injection in mice bearing either AR42J or HEK293-hsst2 tumors, both tracers efficiently and specifically localized in the implants. Whereas 67Ga-DOTA-TOC exhibited higher tumor values, 67Ga-DATA-TOC cleared faster from background tissues. These findings support the suitability of the newly introduced bifunctional chelator DATA as a reliable, quick and convenient means for labeling medically relevant vectors with the PET radiometal 68Ga.

MeSH terms

  • Animals
  • Biological Transport
  • Chelating Agents / chemistry*
  • HEK293 Cells
  • Humans
  • Mice
  • Octreotide / analogs & derivatives*
  • Octreotide / chemistry
  • Octreotide / metabolism
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / metabolism
  • Positron-Emission Tomography*
  • Radioactive Tracers

Substances

  • 68Ga-octreotide, DOTA(0)-Tyr(3)-
  • Chelating Agents
  • Organometallic Compounds
  • Radioactive Tracers
  • Octreotide