TheraSphere® (Yttrium-90) on Hepatocellular Carcinoma (HCC)

Introduction

TheraSphere® is Yttrium-90 microspheres radioembolization useful for liver cancer treatment and used generally to treat patients with hepatocellular carcinoma (HCC) and liver metastases (1).  In this paper, we become to discuss it, how to activate Yttrium-90 on the hepatocellular carcinoma, information of nuclide, radiation and the half-life. We also will analyze physiological features of Yttrium-90 on hepatocellular carcinoma cells and its side effects on the patient.

How to activate Yttrium-90 on hepatocellular carcinoma

TheraSphere (Yttrium-90 microspheres) are radioactive particles as a form of radiation treatment for unresectable HCC. TheraSphere is supplied in 0.5 mL of sterile, pyrogen-free water contained in a 0.3-mL V-bottom vial secured within a 12-mm clear acrylic vial shield. Yttrium-90 microspheres are administered by intra-arterial hepatic injection preferentially flow to tumor (Figure 1.), to patients with unresectable HCC who can have appropriately positioned hepatic arterial catheters (2).

           

Figure 1. Yttrium-90 microspheres are injected into the hepatic arteries preferentially flow to tumor (5).

The Yttrium-90 microspheres are trapped in tumors at the precapillary alveolar level. Patients can be released after infusion of the microspheres, since the Yttrium-90 decays only by beta-emission. Beta radiation is delivered internally to tumor at site of active growth. After administration, the bremsstrahlung radiation (electromagnetic radiation) is produced from the beta minus-interaction in the body, can be imaged and used to determine qualitative distribution in the liver (1).

A suspension of appropriately calibrated Yttrium-90 microspheres injected via the hepatic artery preferentially lodge in the peritumoral vessels, a process termed embolization, by which tumors are deprived of their nutrient arterial supply (3).

Information of nuclide, radiation and half-life

TheraSphere consists of nonbiodegradable glass microspheres (mean diameter of 25 μm) with yttrium-90 as an integral constituent of the glass. Yttrium-90 have the element´s atomic number (Z=39) and number of neutrons (N=51) and the atomic mass (A=90) (1).  Yttrium-90 is a pure beta emitted radionuclide, produced by neutron and decays to stable zirconium-90 with a physical half-life of 64.1 hours (2.67 days). The average energy of beta emission from the yttrium-90 is 0.9367 MeV, with a mean tissue penetration of 2.5 mm and a maximum of 10 mm (2).

One gigabecquerel (1GBq or 27mCi) delivers a total absorbed radiation dose of 50Gy/kg of tissue or per kilogram of targeted liver tissue provides a dose of 50Gy. In therapeutic use, in which the isotope decays to infinity, 94% of the radiation is delivered in 11 days (3).

Physiological Features of Yttrium-90 Microsphere

TheraSphere (MDS Nordion, Ottawa, Ontario, Canada) consists of millions of microscopic, radioactive glass Yttrium-90 microspheres (20–30 micrometers in diameter) with yttrium-90 as an integral constituent of the glass (3). The Yttrium-90 microspheres are not biodegradable; they decay only by a pure beta-emission, produced by neutron bombardment of Yttrium-90 in a reactor with a mean tissue penetration of 2.5 mm (2).

The Yttrium-90 microsphere is a high energy beta-emitter, would create a zone of radiation exposure confined to the vicinity of the tumor while maintaining nontumorous hepatic parenchymal exposure to tolerable levels. This forms the premise for radioembolization, also known as selective internal radiation therapy or microsphere brachytherapy (3). In clinical practice, millions of microspheres, measuring 30 micrometers in diameter incorporating yttrium-90, are injected via an intra-arterial catheter to the hepatic arterial supply of the tumor (3).

In patients with non-compromised liver function, the liver can tolerate 30 to 35Gy (1Gy represents the energy absorbed from ionizing radiation equal to 1 J/kg of tissue) when it is presented via uniform radiation fields with conventional fractionation (2).

Characteristics of yttrium-90 Microspheres are shown in table 1. as following (3, 4).

Table 1. Characteristics of Yttrium-90 Microsphere
Parameter	Glass
Trace name	ThereSphere® (MDS, Nordion, Canada)
Radioactive form	90Y (Yttrium-90)
Diameter	20-30 μm
Specific gravity	3.6 g/dL
Activity per particle	2500 Bq
Average number of  microspheres per administered activity	1.2-8 million
Material	Glass with Yttrium-90 in matrix
Liver tolerance radiation dose	30-35 Gy
FDA Approved	HCC
Recommended dose for liver tumor	2.0-3.0 GBq

           

           Yttrium-90 microspheres can be delivered in a local as segmental or sub-segmental, regional (lobar via the left or right hepatic artery), or whole-liver (via proper hepatic artery) manner, resulting in high radiation doses to arterial-fed tumors while sparing the liver parenchyma, which receives most of its blood supply from the portal vein. This method of radiation treatment provides a safety margin by distributing the radiation in a partial liver volume while treating tumors with tumoricidal doses of radiation. Yttrium-90 microsphere injection provides millions of scattered point sources of radioactivity, as opposed to the uniform fields of external beam radiotherapy. This difference in field properties for a given measure of radiation absorbed dose results in different biological effects (2).

The Side effects

Radioembolization is not without complications; it may lead to post-radioembolization syndrome which includes fatigue, nausea, vomiting, anorexia, fever, abdominal pain and cachexia. More serious adverse events include radiation induced liver toxicity, vascular injury when introducing the catheter, radiation pneumonitis from microspheres shunting around the liver and into the lungs, and gastrointestinal tract ulceration (4).

Absolute contraindications for the use of ⁹⁰Y microspheres include pretreatment with ^99mTc macroaggregated albumin scan demonstrating significant hepatopulmonary shunts, and inability to prevent deposition of the microspheres to the gastrointestinal tract with modern catheter techniques (4).

References

1.      Paul E. Christian, Kristen M. Waterstram. Nuclear Medicine and PET/CT: Technology and Techniques. 7^thEd. Hardcover – March 18, 2011.

2.      Geschwind JF, Salem R, Carr BI, et al. Yttrium-90 Microspheres for the Treatment of     Hepatocellular Carcinoma. Gastroenterology. 2004 Nov;127(5 Suppl 1):194-205.

3.      Murthy R, Kamat P, Nuñez R, Salem R. Radioembolization of Yttrium-90 Microspheres for Hepatic Malignancy. Semin Intervent Radiol. 2008 Mar;25(1):48-57.

4.      Saad M Ibrahim, Robert J Lewandowski, Kent T Sato, et al. Radioembolization for the treatment of unresectable hepatocellular carcinoma: A clinical review. World J Gastroenterol. Mar 21, 2008; 14(11): 1664-1669.

5.      Figure is taken at. http://zoominmedical.com/cancer-tumor-diagram/