Optimizing the radiosynthesis of [68Ga]DOTA-MLN6907 peptide containing three disulfide cyclization bonds – a GCC specific chelate for clinical radiopharmaceuticals

Anchal Ghai, Baljinder Singh, Mengshi Li, Tamara A. Daniels, Richard Coelho, Kelly Orcutt, G. Leonard Watkins, Jeffrey P. Norenberg, Donna Cvet, Michael K. Schultz

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


In the present study, the effect of radiolabeling conditions on radiolabeling efficiency and achievable specific activity of a DOTA-conjugated highly-lipophilic peptide containing three disulfide cyclization bonds was examined. The peptide is designed to bind specifically (with high affinity) to cell-surface receptor guanylyl cyclase C (GCC), which is universally expressed by colorectal cancer cells. The effect of systematic variation of chemical parameters pH, mass of peptide, acetate buffer concentration (ionic strength), and inclusion of ethanol in the radiolabeling reaction vessel on achievable specific activity and labeling efficiency was examined. In addition, a unique approach to acetone-based elution of 68Ga from an initial cation-exchange pre-concentration column is introduced, which improved radiochemical yield and radiochemical purity. For the evaluation of the acetone-based method, two different post-radiolabeling reverse-phase (C18) approaches to purify the final radiolabeled peptide were tested. These results revealed the potential for peptide degradation via the cleavage of disulfide cyclization bonds to form free thiols when using one of these C18 cartridges. The final optimized procedure enabled radiolabeling efficiency of greater than 99% and specific activity greater than 35 MBq/nmole in less than 30 min. The optimized parameters were amenable to the use of an automated 68Ge/68Ga generator and fluid-handling system for clinical production of the GCC receptor-specific [68Ga]DOTA-MLN6907 peptide. The chemical characteristics of individual peptides govern the most appropriate radiolabeling conditions for the preparation of radiopharmaceuticals.

Original languageEnglish (US)
Pages (from-to)333-341
Number of pages9
JournalApplied Radiation and Isotopes
StatePublished - Oct 2018
Externally publishedYes


  • Automated synthesis
  • DOTA peptides
  • Gallium 68
  • Guanyl cyclase-c ligands

ASJC Scopus subject areas

  • Radiation


Dive into the research topics of 'Optimizing the radiosynthesis of [68Ga]DOTA-MLN6907 peptide containing three disulfide cyclization bonds – a GCC specific chelate for clinical radiopharmaceuticals'. Together they form a unique fingerprint.

Cite this