Ionizing radiation is a highly effective, cytotoxic modality for cancer treatment, but has only limited use for metastatic disease applications. An emerging modality for targeted therapy involves delivering alpha (α) or beta (β) emitting radionuclides directly to a disease site. α-particles have a higher linear energy transfer and shorter track than β-particles, which confines them to the tumor microenvironment and renders them a more cytotoxic payload for targeted therapy. Lead-212, ²¹²Pb, which itself is a β-emitter, has been termed an in vivo α-particle generator because it produces two α-emitting daughters through its radioactive decay chain. ²¹²Pb is typically separated from its parents, specifically ²²⁴Ra and ²²⁸Th, by column separation. This process requires time and specialized equipment, and it poses an exposure risk to personnel. To avoid lengthy preparation processes, one proposed method uses ²²⁰Rn emanation to collect ²¹²Pb. In this technique, ²²⁰Rn is collected from a ²²⁸Th solid or liquid source as a gas. ²²⁰Rn can then decay and deposit ²¹²Pb free of any parent isotopes. 
Here, we designed a purification technique where ²²⁰Rn gas can be collected from a ²²⁸Th source via a dual syringe system, which is automated to extract at specified timepoints to reduce handling time. The syringes synchronously push and pull the gas out of the source vial, and this is repeated with a defined time in between each push/pull cycle. Once the ²²⁰Rn gas (t1/2 = 55.6 s) has decayed, ²¹²Pb (t1/2 = 10.64 hours) is found on the surface of each of the two syringes ready for radiolabeling. In this work, it is shown that the proposed generator is able to produce high purity  ²¹²Pb in fair yield and minimal handling time.
In order to optimize the yield of ²¹²Pb from the generator, different operating conditions were examined. First, autoradiography images of the collection syringes were taken in order to determine the location of the ²¹²Pb within the syringe. These images showed that some of the activity translocates with the plunger of the syringe, meaning that the syringes should not be fully compressed during the push/pull cycles of operation. Different times (1 minute to 10 minutes) in between each push/pull cycle of the generator were also examined over a set period of time both experimentally and with a developed model. It was determined through both modeling and experiment that a shorter wait time in between each cycle results in a higher yield.
The quality of the generated ²¹²Pb was assessed using three different instruments: a high purity Germanium detector (HPGe), a gamma counter, and a liquid alpha spectrometer. A sample of ²¹²Pb was measured on each instrument for a total of seven days, and the resulting data was fit to a single-phase decay curve. This was repeated three times for each instrument, and a different batch of generator produced ²¹²Pb was used for each of the measurements. All three methods demonstrated the production of high purity ²¹²Pb (t1/2 = 10.67±0.27 hours), with no indication of emissions from parent isotopes, making it suitable for use with radiopharmaceuticals. The purity of the ²¹²Pb was also evaluated by radio thin layer chromatography (TLC). Using DGA chromatographic paper, ²¹²Pb and ²¹²Bi were able to be separated, confirmed through half-life and HPGe measurement.
Overall, this generator system is able to produce a reasonable yield of ²¹²Pb in high-purity and avoids any lengthy purification steps. Future work will involve testing a targeted ²¹²Pb therapy in an in vivo model and further enhancing the yield. 

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Figure 1. (A) Decay chain of ²²⁸Th. ²²⁰Rn (red) is a noble gas and has a 55.6 second half-life. Collecting this gas from a ²²⁸Th source and allowing it to decay will yield the desired ²¹²Pb and its alpha-emitting daughters (blue). (B) The generator collects the ²²⁰Rn via a dual-syringe system. The desired ²¹²Pb is washed from the walls of the syringe. (C) A representative decay curve acquired from a gamma counter measurement, showing the sample having a 10.55-hour half-life, demonstrating the production of high-purity ²¹²Pb. (D) Autoradiography image of an uncompressed (top) and compressed (bottom) syringe showing ²¹²Pb moves with the plunger during generator operation.

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