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Hall et al. Hepatoma Res. 2026;12:20 Page 3 of 15

Table 1. Comparison of commercially available yttrium-90 microsphere products
Glass microspheres (TheraSphere ) Resin microspheres (SIR-Spheres®)
TM
Manufacturer Boston Scientific, Marlborough, MA Sirtex Medical Inc., Wilmington, MA
Microsphere size 20-30 μm 22-42 μm
Isotope incorporation Y-90 integrated within a glass matrix Y-90 on resin surface
Specific gravity High Low
activity per sphere at calibration 2,500 Bq 50 Bq
Activity per sphere at treatment 100-1500 Bq 52-148 Bq
Time of calibration Prior to treatment Day of treatment or up to 3 days after
Number of spheres per 3 GBq 1.2 million 44 ± 2.6 million
Mean tumor-absorbed dose 197-794 Gy (varies by technique) 73-308 Gy (varies by technique)
Tumoricidal dose for HCC 205 Gy 100-120 Gy
Fewer particles reduce embolic effects; suitable for Better distribution in larger tumors with high arterial
Clinical advantages
portal vein invasion and radiation segmentectomy flow
Gastrointestinal toxicity risk Lower risk of GI tract injury Higher risk of GI ulceration due to more particles
Radiation pneumonitis threshold Higher dose tolerance (~ 41 Gy) Lower dose tolerance (~ 21 Gy)
Y-90: Yttrium-90; Bq: becquerel; GBq: gigabecquerel; Gy: gray; HCC: hepatocellular carcinoma [15-22] .

substantially in their physical and radiobiological characteristics, which influence their clinical applications
and dosimetric properties.

Glass microspheres (TheraSphere™) have Y-90 integrated within the glass matrix, with a higher specific
gravity and significantly higher activity per sphere (2500 Bq at calibration, 100-1500 Bq at treatment). Due to
the higher activity per particle, fewer microspheres are required to deliver a given radiation dose
(approximately 1.2 million spheres per 3 GBq), which may reduce embolic effects. Glass microspheres are
calibrated prior to treatment and are available in 3-20 GBq vials. TheraSphere™ has received regulatory
approval in the United States, the European Union, and other major markets for the treatment of HCC .
[15]

Resin microspheres (SIR-Spheres®) have Y-90 bound to the resin surface, with lower specific gravity and
lower activity per sphere (50 Bq at calibration, 52-148 Bq at treatment). Because of the lower activity per
particle, more microspheres are needed to deliver equivalent radiation doses (approximately 44 ± 2.6 million
spheres per 3 GBq vial), which may provide better distribution in larger tumors with high arterial flow. Resin
microspheres are calibrated on the day of treatment or up to three days afterward and are available in 3 GBq
vials. SIR-Spheres® has received regulatory approval in multiple jurisdictions worldwide, initially for
colorectal liver metastases and subsequently for HCC in many regions .
[15]

The choice between glass and resin microspheres depends on multiple factors, including tumor
characteristics, vascular anatomy, and treatment goals. Glass microspheres may be more suitable when early
stasis or reflux is a concern, in the setting of portal vein invasion, and for radiation segmentectomy, because
fewer particles are required . Resin microspheres may be preferable for larger tumors and those with high
[16]
arterial flow . Studies comparing the two products have shown different dosimetric profiles, with glass
[16]
microspheres typically delivering higher tumor-absorbed doses [mean, 197 gray (Gy) vs. 73 Gy for resin],
though clinical outcomes in terms of tumor response and toxicity appear similar when appropriately
dosed [17,18] .

An emerging alternative product is Holmium-166 (Ho-166) poly(L-lactic acid) microspheres, which is
approved in the European Union and under regulatory review in other jurisdictions . This product offers
[19]
the advantage of direct visualization on single-photon emission computed tomography/computed