General · EdgepediaOctober 20, 202610 min read

Radioembolization

Therapeutic radioembolization is a minimally invasive, catheter-based radiation therapy for liver cancer in which microscopic spheres carrying the radioactive isotope yttrium-90 (Y-90) are injected into the arteries that supply a liver tumor, delivering a high radiation dose to the tumor while sparing normal liver tissue¹. It is also called selective internal radiation therapy (SIRT), transarterial radioembolization (TARE), or intra-arterial brachytherapy¹^•². The National Library of Medicine introduced "Radioembolization, Therapeutic" as a MeSH descriptor on January 1, 2026, defining it as a tailorable technique of infusing Y-90 for hepatocellular carcinoma treatment with continuous restaging³.

Key fact	Detail
Mechanism	Y-90 microspheres injected through the hepatic artery lodge preferentially in tumors, which draw almost all their blood from the hepatic artery while normal liver is supplied mostly by the portal vein⁴
Radiation delivery	About 85% of the Y-90 radiation is delivered within the first week, and less than 0.1% remains one month after the procedure; the microspheres stay in the liver permanently⁵^•⁴
Main devices	Glass microspheres (TheraSphere, Boston Scientific) and resin microspheres (SIR-Spheres, Sirtex Medical), both FDA-approved for unresectable hepatocellular carcinoma⁶^•⁷
Primary uses	Local control of unresectable primary and metastatic liver tumors, downstaging or bridging to transplantation, radiation segmentectomy as sole therapy, and radiation lobectomy to grow the future liver remnant²^•⁴
Versus TACE	In the TRACE randomized trial, median time to progression was 17.1 months with Y-90 glass radioembolization versus 9.5 months with drug-eluting bead chemoembolization (HR 0.36, P = .002)⁸
Dosimetry	In DOSISPHERE-01, personalized dosimetry targeting more than 205 Gy gave objective responses of 76.6% versus 22.2% with standard dosimetry, and median survival of 26.6 versus 10.7 months⁹
Main risks	Gastrointestinal ulceration from non-target embolization, radiation-induced liver disease, and radiation pneumonitis; patients with cirrhosis treated over large liver volumes face a risk of transient or permanent liver failure¹⁰^•⁴

Rationale: hepatic tumor blood supply

The liver has a dual blood supply, receiving blood from the portal vein and the hepatic artery. Beginning in the early 1950s, investigators showed angiographically that liver tumors receive their blood supply from the hepatic artery rather than the portal vein, and further study concluded that hepatic malignancies derive more than 80% of their blood supply from the hepatic artery while normal liver parenchyma receives less than one-third from that route¹¹. In contemporary patient-facing terms, normal liver tissue receives about 75 percent of its blood from the portal vein and about 25 percent from the hepatic artery, whereas a tumor in the liver receives almost all of its supply from the hepatic artery⁴.

This vascular difference is what makes the technique selective. When microspheres are delivered through the hepatic artery, they accumulate preferentially in the tumor rather than the normal liver. The radiation emitted by Y-90 travels only a few millimeters from each microsphere, so high doses accumulate within the tumor while unaffected liver tissue is largely protected⁴.

The isotope and the devices

Yttrium-90 is a beta-emitting isotope used in radiation therapy for certain forms of cancer⁵. Two microsphere platforms dominate clinical use. TheraSphere glass microspheres are made by melting a mixture of yttrium-89 with ultrapure aluminum oxide and silicon dioxide at 1,500 °C, then activating the particles by neutron bombardment, which converts the embedded Y-89 to Y-90; the glass particles are insoluble, nontoxic, and resistant to radiation, with a low rate of leaching⁶. Glass and resin microspheres are similar in size (25 to 35 microns) but differ in the amount of isotope loaded per sphere, which is lower for resin spheres, and in the number of spheres injected per treatment, which is typically lower for glass spheres¹².

A third device, QuiremSpheres, uses holmium-166 and was approved for clinical use in Europe by the European Medicines Agency in April 2015 as a treatment for unresectable liver tumors⁶.

How the procedure is performed

Radioembolization is performed by a specially trained interventional radiologist and commonly requires two sessions. In the first, a mapping angiogram visualizes the abdominal arteries; arteries that supply the stomach or bowel and must be protected from unintentional exposure can be closed with tiny metallic coils. At the end of the mapping session, a dissolvable protein particle carrying a nuclear medicine tracer may be infused to simulate the treatment and confirm, by its distribution in the liver, abdomen, and lungs, that the patient is a candidate. If so, the therapeutic microspheres are administered in a second procedure, typically within two weeks⁴.

The procedure is usually completed within two hours and is often done on an outpatient basis. Because the Y-90 radiation remains largely confined to the liver, patients may be advised to limit close contact with others, particularly children and pregnant women, for the first week while the radiation in the body diminishes⁴. A dose of less than 3 gigabecquerel (GBq) is considered safe in terms of radiation exposure for individuals who may come into contact with the treated patient⁶.

History

The concept of transarterial radioembolization dates to 1951, when Muller and Rossier injected radioactive gold into the pulmonary artery of a patient with lung cancer and shrank the tumor; in the early 1960s isotopes such as phosphorus-32 were used intra-arterially through the hepatic arteries to treat liver tumors⁶. In 1965, Ariel described a technique for infusing Y-90 bonded to 50-micron ceramic microspheres from the celiac artery in four patients with hepatocellular carcinoma, with symptomatic relief in all patients²^•¹³. Simon and colleagues reported in the 1960s on five patients with hepatic neuroendocrine tumors treated with Y-90 loaded onto 15-micron carbonized microspheres²^•¹³.

In 1973, Grady administered 15-micron resin Y-90 microspheres via the arterial route and described a series of 25 metastatic colon cancer patients, with 17 showing an objective reduction in tumor size.¹¹ Work in rats by Meade and colleagues showed that microspheres 15 and 32.5 µm in diameter were three times more likely to lodge in hepatic tumors than in normal parenchyma, while 50 µm microspheres distributed evenly between the two².

The field was initially abandoned because of an increased incidence of adverse effects and lack of commercial interest, then regained clinical interest in trials and achieved established clinical utility in the last 15 years¹⁴. Phase 1 trials in the late 1980s and early 1990s for the newly developed glass and resin microspheres demonstrated safety and early efficacy, leading to a humanitarian device exemption from the FDA in 1999 for glass microspheres in unresectable HCC and, after a phase 3 trial in colorectal liver metastases, FDA premarket approval for resin microspheres in that indication in 2002².

Regulatory status

In March 2021, the FDA granted TheraSphere full premarket approval to control tumors locally when treating solitary growths measuring 1–8 cm across in individuals who have inoperable HCC, Child-Pugh class A (scoring system grading cirrhosis liver-damage severity) cirrhosis, adequately preserved liver function, an absence of macrovascular invasion, and a strong performance status.⁵ In the supporting clinical study of 162 people, 117 experienced a partial or complete response, and for 89 patients the response lasted at least six months⁵.

On July 7, 2025, the FDA approved SIR-Spheres Y-90 resin microspheres for the treatment of unresectable HCC, supported by the DOORwaY-90 study, making SIR-Spheres the radioembolization therapy approved in the United States for both metastatic colorectal cancer of the liver and HCC⁷. The approved indication covers patients with no macrovascular invasion, Child-Pugh A cirrhosis, well-compensated liver function, and good performance status¹⁵.

Clinical evidence and comparisons with TACE

Transarterial chemoembolization (TACE) has been the standard of care for intermediate-stage (BCLC B) hepatocellular carcinoma, and radioembolization has been studied as an alternative². The evidence is mixed. In the TRACE phase II randomized trial, Y-90 glass radioembolization prolonged median time to progression to 17.1 months versus 9.5 months for drug-eluting bead TACE (HR 0.36, P = .002), with median overall survival of 30.2 versus 15.6 months and comparable serious adverse events; the trial was terminated early after the primary endpoint was met⁸. By contrast, the large randomized SARAH and SIRveNIB trials comparing resin microspheres with sorafenib found no significant difference in overall or progression-free survival, despite significantly greater tumor response rates in the SIR-Spheres arms (19% vs 12% in SARAH; 16.5% vs 1.7% in SIRveNIB)¹⁶.

Meta-analyses reflect this heterogeneity. An RCT-only meta-analysis of four trials comprising 169 patients with early- to intermediate-stage unresectable HCC found no significant differences in progression-free survival (HR 0.72), overall survival (HR 0.82), or objective response rate between Y-90 TARE and TACE, but TARE was associated with significantly fewer treatment-related adverse events (OR 0.38, P = 0.005)¹⁷. A broader meta-analysis including randomized and observational studies reached a different conclusion, finding that TARE/SIRT significantly reduced the hazard of death compared with TACE (HR 0.68, 95% CI 0.55-0.86) and improved progression-free or time-to-progression outcomes (HR 0.54), without a significant increase in grade 3 or higher adverse events¹⁸. Guideline positions differ accordingly: EASL guidelines do not recommend Y-90 radioembolization in BCLC B and C patients, citing failure to demonstrate a survival benefit versus TACE or sorafenib, while ESMO recommends TARE for patients in exceptional circumstances or with liver-confined disease for which TACE and systemic therapy are not feasible²^•¹⁹.

Dosimetry and technique variants

Personalized dosimetry has become a central theme. The TRACE trial and earlier randomized comparisons used standard dosimetry, which yields inferior results compared with personalized dosimetry aiming at more than 205 Gy to the targeted area⁹. In the DOSISPHERE-01 trial, patients with unresectable HCC randomized to personalized dosimetry had significantly improved objective responses (76.6% vs 22.2%), downstaging to surgical treatments (35% vs 3.5%), and median survival (26.6 vs 10.7 months) compared with standard dosimetry⁹. The National Comprehensive Cancer Network acknowledges radioembolization in some patients with advanced HCC and recommends a tumor dose of more than 205 Gy, or more than 400 Gy when treatment is selective¹⁹.

Technique variants have expanded the treatment's uses. Radiation segmentectomy delivers very high-dose, ablative radioembolization to a small liver volume and can serve as the sole treatment for a tumor⁴. Radiation lobectomy infuses microspheres to both the tumor and the liver portion a surgeon intends to remove; over three to six months the treated lobe shrinks while the untreated lobe grows, reducing the chance of postoperative liver failure⁴. Y-90 is also used to downstage patients for curative treatments and to provide tumor control as a bridge to transplant or resection².

Safety

The most common relevant complication is gastrointestinal ulceration caused by non-target embolization of Y-90 microspheres into the gastrointestinal tract¹⁰. Early studies also reported elevation of liver enzymes, radiation pneumonitis, radiation hepatitis (renamed radioembolization-induced liver disease, REILD), and gastrointestinal ulceration; some early-trial patients developed myelosuppression and died from leaching of yttrium from the microspheres with deposition in bone marrow, a problem that drove the development of yttrium-binding techniques in the late 1980s and early 1990s¹¹. Patients with underlying liver disease such as cirrhosis who receive treatment to large liver volumes face a risk of transient or permanent liver failure⁴. Radioembolization is not recommended in cases of severe liver dysfunction or an unfavorable mapping angiogram or nuclear medicine simulation⁴.

References

Topic: Encyclopedia › Life and health › Human health and medicine › Clinical assessment and procedures › Radiotherapy techniques

Initially written Oct 20, 2026

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