Our radiochemistry team has successfully radiolabeled over 300 biological agents, 500 small molecules and submitted 80 INDs for clinical use of novel radiotracers. This wide range of chemical entities has included CNS-penetrant small molecules, monoclonal antibodies, PSMA-targeted peptides, intrathecally administered molecules, virus and live cell labeling, and heart and blood targeting agents.
In addition to radiochemistry services, we also offer ligand design capabilities and medicinal chemistry support for optimization and synthesis of new ligands. This includes a in-house organic synthesis lab and partnered CROs for outsourcing DMPK analysis. In addition to in vitro screening, we also perform in silico virtual screening of existing compound libraries to aid in your ligand selection processes.
Across our multiple sites, we offer the following services for radiotracer support:
- Manufacturing for clinical use according to GMP, USP 823, and CFR part 212
- Deep expertise in automated synthesis module, including GE, Eckert and Zeigler, and ORA systems
- Wide range of chemotype handling, from amino acids/sugars to macromolecules and viruses
- Numerous purification methods including HPLC, spin-column and solid-phase extraction
- Ga-68 generator on site
- Siemens Cyclone cyclotrons for C-11 and F-18 production
- Rapid method transfers between Invicro sites
- Shipping of manufactured tracers to off-site scanning facilities
- Outsource tritiation of reagents
In addition to manufacturing capabilities, we provide the following associated quality control services:
- HPLC methodology including RP, HYNIC, SE, IE and UPLC
- In-house development of bioactivity and immunoreactivity assays
- Full metabolite analysis (blood, urine, and brain) to support modeling needs
- Cell binding, tissue binding and cell internalization assay method development
- CMP panel/urine analysis for monitoring metabolic health
- UV/Vis spectrophotometer
- GC for residual solvent
- SDS-page electrophoresis
- Gamma counters for tissue analysis
- Dose calibrator and multi-channel analyzers
- Radio-TLC scanners
Invicro has experience working on projects with common SPECT/PET isotopes including:
Common SPECT Isotopes
Common PET Isotopes
Other Available Isotopes
In addition to the above isotopes, we also support conjugation with fluorophores as well as ‘cold’ radiolabeling with non-radioactive elements.
Invicro has the capabilities to run small molecule ligand development projects either by consulting on the utilization of existing sponsor-derived ligand libraries or by manufacturing custom precursors and standards. For existing ligand libraries, we use our proprietary virtual in silico screening services or medical chemistry expertise to guide ligand design for optimization of radiolabeling and PK/PD requirements. When manufacturing custom precursors, we have an in-house organic synthesis laboratory and a partnership with MedChemImaging.
Additionally, we have used our in-house capabilities to design our own novel ligands to meet sponsor needs, including a PDE10A ligand (MNI-659), an SV2A ligand (MNI-1126), an αVβ6 integrin receptor (IMAFIB), and two adenosine 2A receptor ligands (MNI-444 and MNI-420). Click here to view our case study on the development of our two A2a receptor ligands.
To incorporate radioatoms into biomolecules, several approaches have been utilized at Invicro. These include:
- Direct iodination of tyrosine or histidine residues using iodogen or Chloramine-T
- Indirect radiohalogenation of lysine residues using SFB, SIB, or Bolton-Hunter reagents
- Direct radiometallation of chelator-conjugated biomolecules, most commonly using DOTA, NOTA, DFO, DTPA, and MAG3 chelators.
- Indirect radiometallation using Tz/TCO or DABCO/azine click chemistry
A stability assessment and bioactivity assay are generally performed post-synthesis to determine the impact of the radioatom incorporation. Stability assessments generally include incubation of the radiolabeled biomolecule in serum, plasma, or whole blood at 37oC as a surrogate for in vivo stability and the radiochemical purity of the compound assessed over time using HPLC.
Bioactivity assays typically consist of incubation of the labeled biomolecule with its intended antigen or binding partner and subsequent assay of the binding efficiency. Click here to view our case study that provides details on iodination of an adeno-associated virus (AAV).
In addition to our in-house radiochemistry services we also provide oversight of clinical manufacturing from external sites. This includes production and shipment from our New Haven site to support clinical studies with F-18 based tracers in the local New England area and further for longer lived isotopes.
We also offer access to and setup of a worldwide network of radiotracers manufacturers. This includes a one-time setup of radiotracer manufacturers outside of the Invicro-managed network for both established radiotracers and in-house optimized chemistry processes. This is achieved by bringing the chemistry manufacturing to one of our GMP sites before sending our technology transfer teams to the sponsor-identified site to set up the manufacturing process.
Invicro is currently working with 8 commercial PET manufacturers to provide PET radioligands to imaging sites across the world. These include sites in the U.S., EU, Australia, and South America, with further sites to be added soon.. We also have experience working with external radiochemistry manufacturers to optimize and bring new tracers to registration as NDA for commercial use.