**3. Current applications of 68Ga-radiopharmaceuticals**

Currently gallium-68 is most widely used in the diagnosis of prostate cancer in the form of [68Ga]Ga-PSMA-11, respectively. [68Ga]Ga-PSMA-617 together with [ 177Lu]Lu-DOTA-PSMA-617 forms a theranostic couple, which is very well suited for the diagnosis or treatment of prostate cancer as the 68Ga/177Lu-radiolabelled tracers show a very similar biological behavior. Due to similarities in chemical behavior, identical (in case of PSMA-617) precursors can be radiolabelled using the same or similar equipment, synthesis and quality control methods [14].

The second, but longest known and best evaluated, 68Ga theranostic pair is used for neuroendocrine tumors in combination with various somatostatin analogs. The three most widely used analogs of somatostatin with gallium-68 are [68Ga] Ga-DOTA-TOC, [68Ga]Ga-DOTA-TATE, [68Ga]Ga-DOTA-LAN or [68Ga]Ga-DOTA-NOC [15]. As a therapeutic counterpart, yttrium-90 and lutetium-177 are used.

Besides these two main applications of gallium-68, a variety of studies work on the extension of the application scope.

For imaging of insulinoma pancreatic islets, several versions of 68Ga-radiopharmaceuticals based on Exendin-4, a glucagon-like protein-1 receptor agonist, exist and it was demonstrated that [68Ga]Ga-DOTA-exendin-4 localizes insulinoma significantly better than 111In-radiolabelled radiopharmaceuticals [16].

Integrin αvβ3 and gastrin-releasing peptide receptor (GRPR) are usually overexpressed in human breast cancer, prostate cancer, breast cancer, colorectal cancer, pancreatic cancer, glioma, lung cancer, ovarian cancers, endometrial

cancers, renal cell cancer and gastrointestinal stromal tumors. An amphibian homolog of the mammalian gastrin-releasing peptide bombesin was intensively investigated, also radiolabelled with gallium-68, for imaging of GRPR. For integrin αvβ3, specific imaging probes usually use the peptide arginine-glycine-aspartic acid (RGD). For imagine of GRPR, several radiopharmaceuticals based on gallium-68 were proposed, in particular [68Ga]Ga-BBN-RGD for breast cancer imagine [17], [ 68Ga]Ga-NOTA-Aca-BBN for glioma imagine [18], [68Ga]-NOTA-DUPA-RM26 for prostate cancer imagine.

Another promising area of application of 68Ga-based radiopharmaceuticals is the labeling of human epidermal growth factor receptor family (HER2) [19] and carcinoembryonic antigen (CEA) [20].

Even though gallium-68 is a very convenient radionuclide for use in radiopharmacy, it is widespread in radiopharmaceuticals in comparison with other diagnostic isotopes. But usability and the commercially availability of generator simplified research and motivated developments with a view to a broad routine application.
