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Review
. 2021 Jun 29;26(13):3966.
doi: 10.3390/molecules26133966.

Microspheres Used in Liver Radioembolization: From Conception to Clinical Effects

Philippe d'Abadie  1 , Michel Hesse  1 , Amandine Louppe  1 , Renaud Lhommel  1 , Stephan Walrand  1 , Francois Jamar  1
Affiliations
Review

Microspheres Used in Liver Radioembolization: From Conception to Clinical Effects

Philippe d'Abadie et al. Molecules. .

Abstract

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.

Keywords: dosimetry; liver radioembolization; radiolabeled microspheres.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Particle size distribution for resin, glass, PLLA microspheres and MAA particles. Figure 1 was made by rescaling graphs derived from the analyses of Bakker et al. [30], Bult W. [31] and Gupta et al. using iron labeled glass microspheres [32].
Figure 2
Figure 2
Amount of glass microspheres injected in pig livers as a function of time from microsphere calibration (4, 8, 12 or 16 days), resulting in spheres of different specific activity and concentrations. Reprinted from European journal of nuclear medicine and molecular imaging with permission of Springer Nature (Eur. J. Nucl. Med. Mol. Imaging 2020, 47, 816–827).
Figure 3
Figure 3
Artistic rendering of microscopic microsphere deposition at day 4 post-calibration (a), 8 post-calibration (b) and 12 post-calibration (c). Increased homogeneity of absorbed dose is apparent for glass microspheres injected at day 12 post-calibration (e.g., 193 Bq/microsphere, 5558 microspheres/mL). The proportion of the liver receiving a dose higher or equal to 40 Gy (red and yellow colors) was higher for glass microspheres injected at day 12 post-calibration (c). Reprinted from European journal of nuclear medicine and molecular imaging with permission of Springer Nature (Eur. J. Nucl. Med. Mol. Imaging 2020, 47, 816–827).
Figure 4
Figure 4
Examples of two HCC tumors treated with glass microspheres with similar mean absorbed doses (94 and 95 Gy) but very different dose distributions (personal data). One tumor (dotted line) received a very low dose in a large part of the tumor volume (more than 5 Gy in 66% of the tumor volume), and was in radiological progression two months later. The other tumor (solid line) received a high dose in a large part of the tumor volume (more than 69 Gy in 66% of the tumor volume) and was in radiological response two months later. Note that the cluster with the highest local dose was found in the non-responding tumor (>500 Gy) because of the major heterogeneous distribution.
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