Cold Kit Labeling: The Future of 68Ga Radiopharmaceuticals?

Abstract

Over the last couple of decades, gallium-68 (⁶⁸Ga) has gained a formidable interest for PET molecular imaging of various conditions, from cancer to infection, through cardiac pathologies or neuropathies. It has gained routine use, with successful radiopharmaceuticals such as somatostatin analogs ([⁶⁸Ga]Ga-DOTATOC and [⁶⁸Ga]GaDOTATATE) for neuroendocrine tumors, and PSMA ligands for prostate cancer. It represents a major clinical impact, particularly in the context of theranostics, coupled with their ¹⁷⁷Lu-labeled counterparts. Beside those, a bunch of new ⁶⁸Ga-labeled molecules are in the preclinical and clinical pipelines, with some of them showing great promise for patient care. Increasing clinical demand and regulatory issues have led to the development of automated procedures for the production of ⁶⁸Ga radiopharmaceuticals. However, the widespread use of these radiopharmaceuticals may rely on simple and efficient radiolabeling methods, undemanding in terms of equipment and infrastructure. To make them technically and economically accessible to the medical community and its patients, it appears mandatory to develop a procedure similar to the well-established kit-based ^99mTc chemistry. Already available commercial kits for the production of ⁶⁸Ga radiopharmaceuticals have demonstrated the feasibility of using such an approach, thus paving the way for more kit-based ⁶⁸Ga radiopharmaceuticals to be developed. This article discusses the development of ⁶⁸Ga cold kit radiopharmacy, including technical issues, and regulatory aspects.

Keywords: cold kit; gallium-68; molecular imaging; positron emission tomography (PET); radiolabeling; radiopharmaceuticals.

Figure 1

Radiopharmaceutical grade germanium-68 (⁶⁸Ge)/gallium-68 (⁶⁸Ga) generators from left to right: Galliapharm®, Galli Ad®, and GeGant®.

Figure 2

Chelates commonly used with ⁶⁸Ga.

Figure 3

Typical automated procedure for ⁶⁸Ga labeling of a DOTA peptide [adapted from (106)].

Figure 4

Procedure for the preparation of ⁶⁸Ga-HBED-CC-PSMA-11 (Telix Pharmaceuticals).

Figure 5

Comparison of procedures for Somakit TOC® labeling with 2 different commercial generators [(A). Galliapharm (Eckert & Ziegler) GalliAd (IRE Elit); (B). GalliAd® and IRE Elit) (116).

Figure 6

(A) Comparison of HPLC profiles of automated (blue) and cold kit-based (black) labeling of [⁶⁸Ga]Ga-HBED-CC-PSMA-11. (B,C) Comparison of 2 ⁶⁸Ga-PSMA-11 PET/CT acquisitions rated as good quality using ⁶⁸Ga-PSMA-11 synthetized with sterile cold kit (B) and ⁶⁸Ga-PSMA-11 synthetized with automated module (C). (B,C) from (126).