**7.1 Manual**

The manual radiolabeling approach is a leftover from times, where gallium-68 was mainly used for research purpose, with lower 68Ga-activities and not in a clinical setting for patient care. It is widely used in research and development of new tracers [11–13, 29, 30, 45–51]. Its main advantage is full control over the complete process (pH, time and temperature) and the possibility to easily access radiolabeling kinetics.

Due to its general setup, this method is not suitable and indented for clinical use. Nevertheless, before the introduction of module systems or the cold kits, it was a long time, the only available method.

In general (**Figure 4**), the first step is the preparation of the reaction mixture by mixing [68Ga]GaCl3 with a suitable buffer in the required pH range and the radiolabeling precursor. Here, the purified cyclotron-produced, generator eluate or post-processed gallium-68 can be used.

Then, the reaction vial is incubated to form the 68Ga-complex. Reaction period and reaction temperature are selected in accordance to the kinetics of the complex formation of gallium with the used chelator.

After the reaction, the reaction mixture can be purified using, for example, solid phase extraction from, for example, free gallium-68 and residual germanium-68 impurities.

In the final step, the 68Ga-radiopharmaceutical is sterile filtrated and formulated in the product vial (**Table 2**).
