Expanding ⁶⁸Ga radiolabeling capacity: off-label use of PSMA-11 single vial cold kits through aliquoting and dual...

Prostate cancer is a highly prevalent malignancy, and PET imaging targeting prostate-specific membrane antigen (PSMA) has become essential for assessing recurrence, metastatic spread and eligibility for radioligand therapy, with a 38% increase in PSMA PET activity reported in France between 2022 and 2023. [⁶⁸Ga]Ga-PSMA-11 prepared from single-vial cold kits such as Locametz^® is now widely used, but kit cost, generator activity decay, and preparation procedures restricted to the marketing authorization dossier can limit the number of patients treated per day. This multicenter study investigated, under GMP conditions, an off-label strategy combining aliquoting of Locametz^® vials with single or dual elutions from GalliaPharm^® and GalliAd^®Ge/⁶⁸Ga generators and compared manual versus automated eluate fractionation. Four main approaches were evaluated: single or double elution for a full kit vial and single or double elution for two aliquots prepared 4-6 h apart, with full quality control according to the European Pharmacopoeia and the Locametz^® summary of product characteristics (SmPC), as well as pharmaco-economic and dosimetric evaluations.

Radiolabeling was effective under all conditions that remained within the kit's buffer capacity. Single-generator labeling of complete vials or aliquots reliably yielded radiochemical purity (RCP) > 98% and stable complexes for 4 h. Aliquoting allowed for two separate preparations from a single Locametz^® kit without compromising RCP. Elutions with dual generators proved efficient when the overall HCl 0.1 M volume was < 2.4 mL, resulting in activities reaching approximately 1.7 GBq with RCP ≥ 98%. High acidity or uneven distribution of aliquots caused pH variations and decreased RCP, causing a restricted number of failures (7%). Radiochemical yields achieved approximately 89% in refined standard procedures. Automated eluate fractionation greatly decreased radiation exposure to hands in comparison to manual handling. Pharmaco-economic evaluation showed significant cost savings per patient, with routine daily capacity ranging from 8 to 16 patients per kit, depending on generator age.

Aliquoting Locametz^® vial and optimizing generator use significantly increase [⁶⁸Ga]Ga-PSMA-11 production capacity. These strategies expand patient throughput and reduce costs of PSMA imaging. They provide a practical solution for centers facing rising PSMA PET demand and limited access to ¹⁸F-PSMA tracers and can be potentially applied to other ⁶⁸Ga cold-kit radiopharmaceuticals.