On the Optimization of the Protocol for Automated Radiosyntheses of [۶۸Ga]Ga-Pentixafor, [۶۸Ga]Ga-FAPI-۴ and [۶۸Ga]Ga-DOTATATE in a Modular-Lab Standard

Objective: The present work describes the automated radiochemical syntheses of different PET tracers like [۶۸Ga]Ga-Pentixafor, [۶۸Ga]Ga-FAPI-۴ and [۶۸Ga]Ga-DOTATATE using optimized single protocol in the non-cassette based Eckert & Ziegler (EZ) Modular Lab (fixed tubing system) without any modification in the inbuilt human machine interface (HMI) software. Recently, PET agents viz. [۶۸Ga]Ga-Pentixafor and [۶۸Ga]Ga-FAPI-۴ are gaining prominence for the diagnosis of overexpressed Chemokine Receptor-۴ (CXCR۴) and Fibroblast Activation Protein (FAP) receptor, respectively, in the microenvironment of numerous cancer types. The promising results observed with the clinical usage of [۶۸Ga]Ga-DOTATATE produced using the automated protocol, provided impetus for the clinical translation of [۶۸Ga]Ga-Pentixafor and [۶۸Ga]Ga-FAPI-۴ using the in-house developed automated radiolabeling protocol.Methods: Herein we report a single radiolabeling protocol for the automated preparation of [۶۸Ga]Ga-Pentixafor and [۶۸Ga]Ga-FAPI-۴ in the non-cassette based EZ Modular-Lab Standard radiochemistry module, without any changes in schematic, graphical user interface (GUI) software and time list, from that used for routine production of [۶۸Ga]Ga-DOTATATE in our centre, since ۲۰۱۵. Physico-chemical quality control and in-vitro stability analyses were carried out using radio-TLC and radio-HPLC.Results: The automated protocol yielded reliable and consistent non-decay corrected (ndc) radiochemical yield (RCY) of (۸۴.۴±۰.۹)% and (۸۵.۵±۱.۴)% respectively, for [۶۸Ga]Ga-Pentixafor and [۶۸Ga]Ga-FAPI-۴, with RCP> ۹۸%, which are comparable to the RCY of (۸۴.۴±۱.۲)% and RCP (۹۹.۱±۰.۳)% for [۶۸Ga]Ga-DOTATATE. The biological quality control studies confirmed the formulations to be of ready-to-use pharmaceutical grade.Conclusion: The consistent and reliable RCY and RCP of multiple ۶۸Ga-labeled PET tracers by single optimized automated radiochemistry protocol exhibits the versatility of the EZ Modular Lab.

Keywords:

[۶۸Ga]Ga-Pentixafor , [۶۸Ga]Ga-FAPI-۴ , [۶۸Ga]Ga-DOTATATE , Modular-Lab Standard , PET/CT