Approaching Gallium-68 radiopharmaceuticals for tumor diagnosis: a Medicinal Chemist's perspective

Nuclear medicine has revolutionized disease diagnosis and treatment, particularly in oncology, by enabling precise imaging and targeted therapies using radiopharmaceuticals. Recently, Gallium-68 (⁶⁸Ga) has emerged as a powerful positron emission tomography (PET) imaging agent, with a growing role in theranostics when paired with ¹⁷⁷Lu for cancer treatment. The ability to obtain ⁶⁸Ga from ⁶⁸Ge/⁶⁸Ga generators, along with its favorable radiochemical and pharmacokinetic properties, has driven an increasing number of clinical applications, which culminated with the approvals of ⁶⁸Ga-DOTA-TOC and ⁶⁸Ga-DOTA-TATE for the treatment of neuroendocrine tumors, and ⁶⁸Ga-PSMA-11 for prostate cancer over the past decade. This review provides a comprehensive overview of ⁶⁸Ga radiochemistry, chelators, and key compounds in clinical trials, highlighting the potential of this radionuclide in precision oncology.