Improved purification of cyclotron [68Ga]GaCl3 for the production of 68Ga radiopharmaceuticals

Abstract

Introduction

Increased demand for NetSpot and Illuccix as requirement to receive the respective Lutathera and Pluvicto radiotherapies, and monitor subsequent response to treatment, have reinforced the need to develop alternative ways of producing gallium-68 (⁶⁸Ga). Building on our efforts to produce ⁶⁸Ga in a liquid target on a GE PETtrace, the goal of this work is to modify the current GE Gallium Chloride cassette using the FASTLab 2 synthesis module to produce [⁶⁸Ga]GaCl₃ equivalent to a 1.85 GBq generator and demonstrate compatibility with FDA-approved kits for production of ⁶⁸Ga-labeled radiopharmaceuticals.

Methods

⁶⁸Ga was produced in a liquid target via the ⁶⁸Zn(p,n)⁶⁸Ga reaction. ⁶⁸Ga was loaded onto various sizes of ZR resins (ZR Load, 0.3 mL, 1 mL, or 2 mL). The loading efficiency was determined using a dose calibrator. After washing with HNO₃, 1.75 M HCl was used to elute the ZR Load resin through various sizes of a second ZR resin (ZR CG, 0 mL, 2 mL, 4 mL). Using 0.5 mL fractions, the elution profile was determined. Compatibility of the [⁶⁸Ga]GaCl₃ with NetSpot and Illuccix kits was investigated. Radiochemical purity (RCP) and 4 h stability were determined using radioTLC and radioHPLC. Using a modified [⁶⁸Ga]GaCl₃ cassette and new FASTLab program, 6 validation preparations were conducted using NetSpot and Illuccix kits for which RCP, stability, sterility and suitability were determined. Dual irradiation of 2 liquid targets was also performed, which was used to simultaneously prepare 1 NetSpot and 2 Illuccix kits by diluting the required activity with 0.1 M HCl.

Results

The commercially available GE Cassette gave low RCP using commercial FDA kits. To optimize this, the loading efficiency onto ZR Load and the ratio of ZR resin used to load the initial activity and subsequent elution were explored. When using a 2:4 ratio of ZR Load to ZR CG, 97.89 % RCP was observed when a 3.8 mL [⁶⁸Ga]GaCl₃ solution was used. For Dotatate validation, 0.55 mL of buffer was added to 4.2 mL of [⁶⁸Ga]GaCl₃ which gave 1.35 GBq of formulated product. For Illuccix validation, [⁶⁸Ga]GaCl₃ was added to 2.5 mL of buffer which gave 1.52 GBq of [⁶⁸Ga]Ga-PSMA-11. Formulated products passed package insert quality control (QC) requirements. When dual target irradiations were performed, 2.84 GBq was delivered to an external vial and used to label 1 NetSpot and 2 Illuccix kits simultaneously, and each kit also met or exceeded established QC criteria.

Conclusion

Methods are reported for using cyclotron-produced ⁶⁸Ga from a liquid target in conjunction with FDA-approved NetSpot and Illucix kits. By employing a 2 mL ZR Load resin with a 4 mL ZR CG resin, adequate resolution between residual ⁶⁸Zn and desired ⁶⁸Ga was achieved. By modifying the FASTLab procedure to retain the final 2.5 mL of eluate from the ZR CG resin, [⁶⁸Ga]GaCl₃ equivalent to a new 1.85 GBq generator was obtained. This was suitable for labeling NetSpot and Illucix kits, resulting in high incorporation of ⁶⁸Ga (RCP >95 %), which has not previously been demonstrated. Delivering [⁶⁸Ga]GaCl₃ into an external vial and diluting with 0.1 M HCl makes it possible to prepare multiple kits simultaneously. These new procedures should facilitate use of cyclotron-produced [⁶⁸Ga]GaCl₃ for clinical production going.