Journal article
Optimizing the radiosynthesis of [68Ga]DOTA-MLN6907 peptide containing three disulfide cyclization bonds – a GCC specific chelate for clinical radiopharmaceuticals
Applied radiation and isotopes, Vol.140, pp.333-341
10/2018
DOI: 10.1016/j.apradiso.2018.08.006
PMID: 30138815
Abstract
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.
•The buffer pH, mass of peptide (concentration), and ethanol concentration are optimized for efficient 68Ga radiolabeling of a GCC specific peptide ligand that contains three disulfide cyclization bonds.•Radiochemical purity of greater than 99% and specific activity of up to 36 MBq/nmole was achieved.•Optimization of the automated synthesis of a 68Ga labeled GCC specific peptide ligand with three disulfide bonds is described.•Degradation of the GCC-specific ligand due to use of a specific C18 purification cartridge type for final purification is found to be associated with breakage of disulfide bonds.
Details
- Title: Subtitle
- Optimizing the radiosynthesis of [68Ga]DOTA-MLN6907 peptide containing three disulfide cyclization bonds – a GCC specific chelate for clinical radiopharmaceuticals
- Creators
- Anchal Ghai - Department of Nuclear Medicine, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, IndiaBaljinder Singh - Department of Nuclear Medicine, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012, IndiaMengshi Li - Department of Radiology, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USATamara A Daniels - Radiopharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USARichard Coelho - InviCRO, LLC, 27 Drydock Avenue, Boston, MA 02210 , USAKelly Orcutt - InviCRO, LLC, 27 Drydock Avenue, Boston, MA 02210 , USAG. Leonard Watkins - Department of Radiology, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USAJeffrey P Norenberg - Radiopharmaceutical Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADonna Cvet - Takeda Pharmaceuticals, 40 Landsdowne Street, Cambridge, MA 02139, USAMichael K Schultz - Department of Radiology, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Applied radiation and isotopes, Vol.140, pp.333-341
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.apradiso.2018.08.006
- PMID
- 30138815
- ISSN
- 0969-8043
- eISSN
- 1872-9800
- Grant note
- name: US National Institutes of Health National Cancer Institute, award: K25 CA172218-01A1
- Language
- English
- Date published
- 10/2018
- Academic Unit
- Radiology; Stead Family Department of Pediatrics; Radiation Oncology
- Record Identifier
- 9984216566802771
Metrics
10 Record Views