This work describes the production of two clinically relevant metal radioisotopes [Formula: see text] and [Formula: see text] with a medical cyclotron by the irradiation of liquid targets. New results are presented for the implementation of this methodology in a fully automated system, using commercially available equipment. Liquid target solutions containing enriched [Formula: see text] and [Formula: see text] were loaded, bombarded and transferred to synthesis modules where a purified solution containing the desired radiometal is obtained and can then be used to further radiolabeling within only one hour after End-Of-Bombardment (EOB). Typical production runs using enriched material lead to the production of 5 GBq and 6 GBq (0.14 MBq/([Formula: see text]Ah ⋅ mg) and 1.5 MBq/([Formula: see text]Ah ⋅ mg)) of [Formula: see text] and [Formula: see text]; although the technique can be used to obtain up to 25 GBq and 40 GBq, respectively, by simply scaling up the amount of the enriched material. Purified solutions containing [Formula: see text] and [Formula: see text] were obtained within 30 min after EOB and used to produce [Formula: see text]-ATSM and [Formula: see text]–DOTA–NOC, respectively, with quality parameters suitable for human use.

Here we report a two-step surface modification methodology to radiolabel small extracellular vesicles (SEVs) with 64 CuCl 2 for PET/MRI imaging. The modification did not change or damage the morphology, surface receptor proteins and internal RNA content. Radiolabeled SEVs could be detected in organs with low accumulation such as the brain (0.4-0.5% ID/g) and their brain location determined by MRI.SEVs are nanovesicles, with sizes ranging between 30 and 200 nm, secreted by cells.

An automated process for the production and purification of radiometals produced by irradiating liquid targets in a medical cyclotron, using a commercially available module, has been developed. The method is suitable for the production and purification of radiometals such as 68Ga, 64Cu and 61Cu through irradiation of liquid targets and is important for producing high specific activity radioisotopes with a substantial reduction in processing time and cost when compared with the solid target approach. The “liquid target” process also eliminates the need for pre- and post-irradiation target preparation and simplifies the transfer of irradiated material from target to hotcell. A 68GaCl3 solution can be obtained in about 35 min with an average yield of 73.9 ± 6.7% in less than 10 mL of volume. 64CuCl2 solutions can be obtained with an average yield of 81.2 ± 7.8% in about 1 h of processing time. A dedicated single-use disposable kit is used on a commercial IBA Synthera® extension module.

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