“NOTA‐PRGD₂ and NODAGA‐PRGD₂: Bioconjugation, characterization, radiolabelling, and design space”

Abstract

This work reports on the development of amide bond bioconjugation for the production of -NOTA and -NODAGA PRGD using batch strategy and microfluidic reactor technology. The final radiolabelling step was fully optimized using Design of Experiments and Design Space approaches, hence targeting robust labelling yields in routine. Optimal labelling conditions were defined in sodium acetate buffer as 168 μg/mL peptide concentration, 4.9 pH, 47.5°C temperature, and 12.5-minute reaction time. Upon optimization, the Gallium-68 radiolabelling was fully automated. All the work was designed to be compliant to the GMP environment and to support the pharmaceutical scale-up.

Toward diagnostic relevance of the αVβ5, αVβ3, and αVβ6 integrins in OA: expression within human cartilage and spinal osteophytes

“…This result would tip the balance toward the selection of NODAGA-PRGD 2 for future clinical studies, as NODAGA presents better chelator properties for 68 Ga as well as a better bioconjugation rate. 32 This work confirms integrin α V β 3 as a specific target of the core PRGD 2 ligand. 23 Moreover, we identified integrin α V β 5 and α V β 6 as additional targets with high affinity for the PRGD 2 ligand, whereas α 5 β 1 was the complex with the lowest affinity (IC 50 ≈ 600 nmol•L −1 ).…”

“…This result would tip the balance toward the selection of NODAGA-PRGD 2 for future clinical studies, as NODAGA presents better chelator properties for 68 Ga as well as a better bioconjugation rate. 32 …”

“…For future clinical applications, another radioisotope (i.e., 68 Ga) could be considered to simplify the PRGD 2 radiolabeling process. 32 During this process, 68 Ga complexation can be achieved either with NOTA or NODAGA chelators, which are known to have different pharmacokinetic properties toward radioligands in vivo. 32 Therefore, we included the characterization of NOTA-PRGD 2 and NODAGA-PRGD 2 in this study to test whether these chelators could affect PRGD 2 affinity for integrins and thereby guide future chelator selection.…”