Introduction Thallium-201 is a radionuclide that has previously been used clinically for myocardial perfusion scintigraphy. Although in this role it has now been largely replaced by technetium-99 m radiopharmaceuticals, thallium-201 remains attractive in the context of molecular radionuclide therapy for cancer micrometastases or single circulating tumour cells. This is due to its Auger electron (AE) emissions, which are amongst the highest in total energy and number per decay for AE-emitters. Currently, chemical platforms to achieve this potential through developing thallium-201-labelled targeted radiopharmaceuticals are not available. Here, we describe convenient methods to oxidise [ 201 Tl]Tl(I) to chelatable [ 201 Tl]Tl(III) and identify challenges in stable chelation of thallium to support future synthesis of effective [ 201 Tl]-labelled radiopharmaceuticals. Methods A plasmid pBR322 assay was carried out to determine the DNA damaging properties of [ 201 Tl]Tl(III). A range of oxidising agents (ozone, oxygen, hydrogen peroxide, chloramine-T, iodogen, iodobeads, trichloroisocyanuric acid) and conditions (acidity, temperature)were assessed using thin layer chromatography. Chelators EDTA, DTPA and DOTA were investigated for their [ 201 Tl]Tl(III) radiolabelling efficacy and complex stability. Results Isolated plasmid studies demonstrated that [ 201 Tl]Tl(III) can induce single and double-stranded DNA breaks. Iodo-beads, iodogen and trichloroisocyanuric acid enabled more than 95% conversion from [ 201 Tl]Tl (I) to [ 201 Tl]Tl(III) under conditions compatible with future biomolecule radiolabelling (mild pH, room temperature and post-oxidation removal of oxidising agent). Although chelation of [ 201 Tl]Tl(III) was possible with EDTA, DTPA and DOTA, only radiolabeled DOTA showed good stability in serum. Conclusions Decay of [ 201 Tl]Tl(III) in proximity to DNA causes DNA damage. Iodobeads provide a simple, mild method to convert thallium-201 from a 1+ to 3+ oxidation state and [ 201 Tl]Tl(III) can be chelated by DOTA with moderate stability. Of the well-established chelators evaluated, DOTA is most promising for future molecular radionuclide therapy using thallium-201; nevertheless, a new generation of chelating agents offering resistance to reduction and dissociation of [ 201 Tl]Tl(III) complexes is required.

The reaction of phosphole/arsole starting materials with a series of halide abstraction reagents afforded their respective phosphenium/arsenium complexes. UV-vis absorption and luminescence studies on these cations showed interesting emission profiles, which was found to be dependent upon counterion choice. The addition of a reductant to the phosphole reagent garnered a dimeric species with a central P-P bond, which when heated was found to undergo homolytic bond cleavage to produce an 11π radical complex. Electron paramagnetic resonance (EPR), supported by density functional theory (DFT) calculations, was used to characterize this radical species.

Background: Multi-tracer PET/SPECT imaging enables different modality tracers to be present simultaneously, allowing multiple physiological processes to be imaged in the same subject, within a short time-frame. Fluorine-18 and technetium-99m, two commonly used PET and SPECT radionuclides, respectively, possess different emission profiles, offering the potential for imaging one in the presence of the other. However, the impact of the presence of each radionuclide on scanning the other could be significant and lead to confounding results. Here we use combinations of 18 F and 99m Tc to explore the challenges posed by dual tracer PET/SPECT imaging, and investigate potential practical ways to overcome them. Methods:Mixed-radionuclide 18 F/ 99m Tc phantom PET and SPECT imaging experiments were carried out to determine the crossover effects of each radionuclide on the scans using Mediso nanoScan PET/CT and SPECT/CT small animal scanners.Results: PET scan image quality and quantification were adversely affected by 99m Tc activities higher than 100 MBq due to a high singles rate increasing dead-time of the detectors. Below 100 MBq 99m Tc, PET scanner quantification accuracy was preserved. SPECT scan image quality and quantification were adversely affected by the presence of 18 F due to Compton scattering of 511 keV photons leading to over-estimation of 99m Tc activity and increased noise. However, 99m Tc: 18 F activity ratios of > 70:1 were found to mitigate this effect completely on the SPECT. A method for correcting for Compton scatter was also explored. Conclusion:Suitable combinations of injection sequence and imaging sequence can be devised to meet specific experimental multi-tracer imaging needs, with only minor or insignificant effects of each radionuclide on the scan of the other.