Increasing attention is given to personalized tumour therapy, where α-emitters can potentially play an important role. Alpha particles are ideal for localized cell killing because of their high linear energy transfer and short ranges. However, upon the emission of an α particle the daughter nuclide experiences a recoil energy large enough to ensure decoupling from any chemical bond. These ‘free’ daughter nuclides are no longer targeted to the tumour and can accumulate in normal tissue. In this paper, we used polymersomes as model carrier to evaluate the retention of recoiling daughters of ²²⁵Ac in vivo, and assessed their suitability as therapeutic agents. Vesicles containing ²²⁵Ac were injected intravenously in healthy mice, and intratumourally in tumour-bearing mice, and the relocation of free ²¹³Bi was assessed in different organs upon the injection [²²⁵Ac]Ac-polymersomes. The therapeutic effect of ²²⁵Ac-containing vesicles was studied upon intratumoural injection, where treatment groups experienced no tumour-related deaths over a 115 day period. While polymersomes containing ²²⁵Ac could be suitable agents for long-term irradiation of tumours without causing significant renal toxicity, there is still a significant re-distribution of daughter nuclides throughout the body, signifying the importance of careful evaluation of the effect of daughter nuclides in targeted alpha therapy.

The combined α-, γ-, and x-ray emitter ²¹³Bi (half-life, 46 min) is promising for radionuclide therapy. SPECT imaging of ²¹³Bi is challenging, because most emitted photons have a much higher energy (440 keV) than common in SPECT. We assessed ²¹³Bi imaging capabilities of the Versatile Emission Computed Tomograph (VECTor) dedicated to (simultaneous) preclinical imaging of both SPECT and PET isotopes over a wide photon energy range of 25-600 keV. Methods: VECTor was equipped with a dedicated clustered pinhole collimator. Both the 79 keV x-rays and the 440 keV γ-rays emitted by ²¹³Bi could be imaged. Phantom experiments were performed to determine the maximum resolution, contrast-to-noise ratio, and activity recovery coefficient for different energy window settings. Additionally, imaging of [²¹³Bi-DOTA,Tyr³]octreotate and ²¹³Bi-diethylene triamine pentaacetic acid (DTPA) in mouse models was performed. Results: Using 440 keV γ-rays instead of 79 keV x-rays in image reconstruction strongly improved the resolution (0.75 mm) and contrast-to-noise characteristics. Results obtained with a single 440 keV energy window setting were close to those with a combined 79 keV/440 keV window. We found a reliable activity recovery coefficient down to 0.240 MBq/mL with 30-min imaging time. In a tumor-bearing mouse injected with 3 MBq of [²¹³Bi-DOTA,Tyr³]octreotate, tumor uptake could be visualized with a 1-h postmortem scan. Imaging a nontumor mouse at 5-min frames after injection of 7.4 MBq of ²¹³Bi-DTPA showed renal uptake and urinary clearance, visualizing the renal excretion pathway from cortex to ureter. Quantification of the uptake data allowed kinetic modeling and estimation of the absorbed dose to the kidneys. Conclusion: It is feasible to image ²¹³Bi down to a 0.75-mm resolution using a SPECT system equipped with a dedicated collimator.