Radiolabelling of peptides for PET, SPECT and therapeutic applications using a fully automated disposable cassette system

Nucl Med Commun. 2011 Oct;32(10):887-95. doi: 10.1097/MNM.0b013e3283497188.

Abstract

Objectives: Radiolabelled somatostatin analogues have found wide clinical use in nuclear medicine for both diagnostic and therapeutic applications. Here, we describe the development of a fully automated synthesis system allowing radiolabelling of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-derivatized peptides with ⁶⁸Ga/¹¹¹In/¹⁷⁷Lu and ⁹⁰Y, meeting radiation safety and pharmaceutical requirements.

Materials and methods: The system consists of a syringe pump, a holder for insertion of a single use multivalve cassette, a heater and a removable radiation shielding. ⁶⁸Ga labelling was performed in acetate buffer and ¹⁷⁷Lu, ⁹⁰Y and ¹¹¹In labelling in ascorbate buffer, respectively, followed by purification on a C18 cartridge and final sterile filtration. Cross-contamination was prevented by using disposable cassettes and also by ensuring pharmaceutical standards. Radiochemical purity (RCP) was determined by instant thin-layer chromatography on silica gel impregnated glass fibres and reversed-phase high performance liquid chromatography.

Results: ⁶⁸Ga-DOTA-peptides were prepared with high RCP (>91%) and radiochemical yields (RCY>80% decay corrected) and ⁶⁸Ge content was less than 0.0001% in all cases. Synthesis time did not exceed 30 min. ¹¹¹In, ¹⁷⁷Lu and ⁹⁰Y labelling of DOTA-peptides resulted again in high yields (approximately 90%) and RCP (approximately 95%) and total synthesis time of less than 45 min. Radiation dose to fingers was considerably reduced when compared with manual labelling procedures.

Conclusion: The described system allows fully automated, aseptic preparation of DOTA-peptides radiolabelled with different radionuclides in high radiochemical yields and pharmaceutical quality suitable for clinical application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Automation
  • Disposable Equipment*
  • Equipment Safety
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Isotope Labeling / instrumentation*
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / therapeutic use
  • Positron-Emission Tomography*
  • Radiometry
  • Robotics
  • Tomography, Emission-Computed, Single-Photon*

Substances

  • Heterocyclic Compounds, 1-Ring
  • Peptides
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid