On the Optimization of the Protocol for Automated Radiosyntheses of [68Ga]Ga-Pentixafor, [68Ga]Ga-FAPI-4 and [68Ga]Ga-DOTATATE in a Modular-Lab Standard.

Abstract

Objectives: The present work describes the automated radiochemical synthesis of different PET tracers like [⁶⁸Ga]Ga-Pentixafor, [⁶⁸Ga]Ga-FAPI-4 and [⁶⁸Ga]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. [⁶⁸Ga]Ga-Pentixafor and [⁶⁸Ga]Ga-FAPI-4 are gaining prominence for the diagnosis of overexpressed Chemokine Receptor-4 (CXCR4) and Fibroblast Activation Protein (FAP) receptor, respectively, in the microenvironment of numerous cancer types. The promising results observed with the clinical usage of [⁶⁸Ga]Ga-DOTATATE produced using the automated protocol, provided impetus for the clinical translation of [⁶⁸Ga]Ga-Pentixafor and [⁶⁸Ga]Ga-FAPI-4 using the in-house developed automated radiolabeling protocol.

Methods: Herein we report a single radiolabeling protocol for the automated preparation of [⁶⁸Ga]Ga-Pentixafor and [⁶⁸Ga]Ga-FAPI-4 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 [⁶⁸Ga]Ga-DOTATATE in our centre, since 2015. 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 (84.4%±0.9%) and (85.5%±1.4%) respectively, for [⁶⁸Ga]Ga-Pentixafor and [⁶⁸Ga]Ga-FAPI-4, with RCP>98%, which are comparable to the RCY of (84.4%±1.2%) and RCP (99.1%±0.3%) for [⁶⁸Ga]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 ⁶⁸Ga-labeled PET tracers by single automated radiochemistry protocol exhibits the versatility of the EZ Modular Lab.