The liver has a dual blood supply, normally 75% of blood is supplied by the portal vein and 25% by the hepatic artery. Hepatic tumors, however, are primarily supplied by the hepatic artery (95% of blood supply).
Hepatic Angiogram Example
An intra-arterial treatment therefore has the benefits of high delivery of the treatment agent to the tumor with low systemic toxicity. Transarterial chemoembolization (TACE) agents have chemotherapy mixed with embolic particles (100-500 μm) producing both ischemia and high concentration of cytotoxic agents. Radioembolization agents have yttrium-90 within tiny spheres (15-60 μm) delivering short range irradiation with minimal embolic effect.
Radioembolization or SIRT (Selective Internal Radiation Therapy) refers to the intra-arterial administration of yttrium-90 containing spheres for treatment of hepatic tumors.
Yttrium-90 is a “pure” β- emitter (>99.9%) with a half life of 64.2 hours, and decays to stable Zirconium-90. β- particles have mean energy of 0.9367 MeV, mean tissue penetration of 2.5 mm, and maximum tissue penetration of 10 mm.
2 FDA approved Y90 agents are commercially available:
The most common involvement of nuclear medicine is the performance and interpretation in the preprocedure Technetium 99m MAA study. This imaging occurs shortly after a planning angiogram, when vascular anatomy is established, branch vessels supplying extrahepatic structures may be prophylactially embolized, and Tc99m MAA is injected at the planned site of treatment.
Goals of the Tc99m MAA study:
Evaluate tumor to nontumor ratio of radiotracer uptake (surrogate for perfusion)
Assess for intrahepatic shunting, manifested by lung activity
Evaluate for extrahepatic visceral perfusion (stomach, duodenum, etc.)
Intrahepatic (arteriovenous) shunting results from abnormal intratumoral blood vessels. This is more common in hepatocellular carcinoma than metastases, and the degree of shunting has been shown to correlate with tumor size/vascularity on other imaging. Shunting is traditionally calculated on planar anterior/posterior images, using the formula:
Extrahepatic visceral perfusion is best detected using SPECT/CT imaging. This can be corrected in the vast majority of cases by angiography techniques (catheter positioning, subselective catheterization, or branch vessel embolization), however nontarget embolization to other viscera is a contraindication to Y90 treatment if not corrected. Perfusion to the stomach or other visceral organs is more common with a left hepatic artery injection.
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The treatment dose of Y90 may be calculated by the department of nuclear medicine, interventional radiology, or radiation oncology. This is often done with the help of a medical physicist.
The dosing method is different for SIR-Spheres and Theraspheres. SIR spheres are may be dosed by an empiric method, body surface area method (most common), or a partition model.
SIR Spheres Dose Calculation
Theraspheres are dosed using a volume-based method, or a partition model in recent publications.
Theraspheres Dose Calculation
Multiple recent studies have shown that partition model dosing, which takes into account the tumor-to-nontumor uptake of MAA on SPECT imaging, results in improved outcomes. (Garin E, et al. J Nucl Med 2015;56:339–346. Demirelli S, et al. Nucl Med Commun 2015;36:340-9.) However strong correlation of MAA uptake and site of treatment on post therapy imaging is not universally observed. (Ilhan H, et al. J Nucl Med 2015;56:1654–60.)
An authorized user is a physician on a U.S. Nuclear Regulatory Commission or Agreement State license who is permitted to use radioactive materials for medical use. In this case the authorized user injects the Y90 agent into the patient. Nuclear medicine physicians, interventional radiologists, or radiation oncologists may serve as the authorized user for Y90 radioembolization.
Post treatment assessment may be performed with either Bremsstrahlung SPECT or PET imaging, which demonstrate the actual distribution in the liver that was treated.
Bremsstrahlung SPECT
German for “braking radiation” or photons produced in this case by interaction of β- particles with matter in the patient
Imaged with medium or high energy collimator with wide window to accommodate the broad range of energies of emitted photons
PET imaging
Y90 has a minute fraction of β+ decay, resulting in 511 keV photons which can be detected by PET imaging
Improved resolution compared to Bremsstrahlung SPECT
These imaging methods allow assessment of absorbed tumor dose, absorbed dose to normal liver parenchyma, and tumor coverage/distribution of treatment.
Braat AJAT, et al. J Nucl Med 2015;56:1079-1087.
Zade AA, et al. Nucl Med Commun 2013;34:1090-1096.
