Inert microspheres, labeled with several radionuclides, have been developed during the last two decades for the intra-arterial treatment of liver tumors, generally called Selective Intrahepatic radiotherapy (SIRT). The aim is to embolize microspheres into the hepatic capillaries, accessible through the hepatic artery, to deliver high levels of local radiation to primary (such as hepatocarcinoma, HCC) or secondary (metastases from several primary cancers, e.g., colorectal, melanoma, neuro-endocrine tumors) liver tumors. Several types of microspheres were designed as medical devices, using different vehicles (glass, resin, poly-lactic acid) and labeled with different radionuclides, ⁹⁰Y and ¹⁶⁶Ho. The relationship between the microspheres’ properties and the internal dosimetry parameters have been well studied over the last decade. This includes data derived from the clinics, but also computational data with various millimetric dosimetry and radiobiology models. The main purpose of this paper is to define the characteristics of these radiolabeled microspheres and explain their association with the microsphere distribution in the tissues and with the clinical efficacy and toxicity. This review focuses on avenues to follow in the future to optimize such particle therapy and benefit to patients.

To determine the factor triggering the sudden surge of daily new COVID-19 cases arising in most European countries during the autumn of 2020. The dates of the surge were determined using a fitting of the two last months of reported daily new cases in 18 European countries with latitude ranging from 39° to 62°. The study proves no correlation between the country surge date and the 2 weeks preceding temperature or humidity but shows an impressive linear correlation with latitude. The country surge date corresponds to the time when its sun UV daily dose drops below ≈ 34% of that of 0° latitude. Introducing reported seasonal blood 25-hydroxyvitamin D (25(OH)D) concentration variation into the reported link between acute respiratory tract infection risk and 25(OH)D concentration quantitatively explains the surge dynamics. Several studies have already substantiated a 25(OH)D concentration impact on COVID-19 severity. However, by comparing different patient populations, discriminating whether a low 25(OH)D concentration is a real factor underlying COVID-19 severity or only a marker of another weakness that is the primary severity factor can be challenging. The date of the surge is an intrapopulation observation and has the benefit of being triggered only by a parameter globally affecting the population, i.e. decreases in the sun UV daily dose. The results indicate that a low 25(OH)D concentration is a contributing factor to COVID-19 severity, which, combined with previous studies, provides a convincing set of evidence.

The 50% normal-tissue complication probability (NTCP) after lobar irradiation of the liver results in highly variable biologic effective doses depending on the modality used: a biologic effective dose for 50% (BED50) of 115, 93, and 250 Gy for external-beam radiotherapy, resin microsphere radioembolization, and glass microsphere radioembolization, respectively. This misunderstood property has made it difficult to predict the maximal tolerable dose as a function of microsphere activity and targeted liver volume. The evolution toward more selective catheterization techniques, resulting in more variable targeted volumes, makes it urgent to solve this issue. We computed by Monte Carlo simulations the microsphere distribution in the portal triads based on microsphere transport dynamics through a synthetically grown hepatic arterial tree. Afterward, the microscale dose distribution was computed using a dose deposition kernel. We showed that the equivalent uniform dose cannot handle microscale dosimetry and fails to solve the discordance between the BED50 values. Consequently, we developed a new radiobiologic model to compute the liver NTCP from the microscale dose distribution. The new model explains all the observed BED50 values and provides a way to compute the hepatic dose-toxicity relationship as a function of microsphere activity and targeted liver volume. The NTCP obtained is in agreement with the data reported from clinical radioembolization studies. The results should encourage interventional radiologists to fine-tune the delivered dose to the liver as a function of the targeted volume. The present model could be used as the backbone of the treatment planning, allowing optimization of the absorbed dose to the tumors.