Y90 Radioembolization Dose Delivery and Radiation Exposure Assessment

Radioembolization using Y90 microspheres is a relatively new therapy option for patients with
hepatocellular carcinoma (HCC) or other metastatic disease. This process requires the
injection of radioactive beta-emitting spheres to delivery a targeted dose to the lesion
resulting in cell death. With this technology comes many questions related to the safety and
handling and usage of these products. This study will focus on three key aspects of dose
delivery using these products.

The first aim will examine radiation exposure to staff that are involved in handling Y90
microspheres. Radiation exposure to employees has only been somewhat addressed with a recent
publication in the European Journal of Nuclear Medicine. Although this work contained key
information for assessing exposure, the methods used were characteristic of european clinics
and do not mirror the typical workflows seen in North American facilities. In this study, we
will use new dosimeter technology to examine radiation exposure to the hands and body of the
following clinical personnel using both TheraSphere and SIR-Spheres technology:

- Nuclear medicine technologists: responsible for drawing up, transporting, and disposal
of Y90 microspheres doses.

- Interventional radiologists: responsible for administration of Y90 microspheres doses

The second aim will examine the use of a modular and portable detector device to provide
real-time monitoring of radiation fields surrounding the microsphere administration systems.
With current workflows, the final confirmation of whether the full dose was delivered is not
assessed until after the procedure is completed and residual vial activities measured. This
work will examine if this type of device might be useful in providing a real-time
determination of whether the prescribed Y90 microspheres dose was fully delivered to the
patient. Detectors will be placed at points throughout the delivery system and data recorded
before, during, and after the injection of Y90. Time activity curves will be generated and
assessed to determine activity levels near the dose vial and through distribution lines as
the dose is injected. We will use various analysis techniques to identify and characterize
the injection to determine if a dose administration was successful prior to removing the
patient from the procedure room.

The third aim will use a modular detector device as well as post-radioembolization PET/CT to
examine leaching of free Y90 following injection of Y90 microspheres. Some degree of leaching
is expected with any labeled product, however, the degree of leaching involved with Y90
microspheres in vivo has yet to be studied in any detail. This pilot study will use two
techniques to assess the impact and degree of leaching during Y90 dose administration.

The first step will use the modular detector device used in aim two of this proposal to
measure radioactivity before, during, and after the Y90 dose administration. Detectors will
be placed near the patient skin surface in close proximity to the lesion(s) being treated, as
well as location distal to the catheter location in other body areas, including the
extremities. Time activity curves will be generated from the data collected which will enable
analysis of on-target and off-target activity. This data may also be used to assess flow
kinetics which may improve isolation of the cause or route of leached Y90 should it be found.

The second step will involve imaging the patients using PET/CT. Typical Y90 radioembolization
focuses on only imaging the liver for assessment of dosimetry following the dose
administration. In this study, we will acquire a longer axial PET/CT covering an anatomical
range from the top of the head to the lower extremities. This is equivalent to a typical
PET/CT protocol used in melanoma imaging. The CT used will be a low-dose CT used only for
anatomical localization and PET attenuation correction while the PET acquisition will only
use the on-board Y90 for imaging and will not add any additional patient dose.

Using these two methods, we hope to monitor and assess leaching both during and after Y90
radioembolization to determine key concerns, such as the following:

- The frequency of detectable levels of leaching

- Physical extent of leaching throughout the body

- Patient radiation dose estimates associated with the leaching phenomenon

Inclusion Criteria:

- All patients undergoing Y90 radioembolization therapy with SIR-Spheres or TheraSpheres
are eligible to participate in this study

- Must be able to schedule and tolerate additional PET/CT imaging following therapy

- Must be able to tolerate additional blood draws before, during, and after the
radioembolization therapy procedure.

Exclusion Criteria:

- Patients that are not candidates for Y90 radioembolization therapy

- Patients that cannot tolerate additional imaging procedures following therapy

- Patients that cannot tolerate the additional blood draws required for this study

- Patients whose schedule does not allow them to remain at the hospital for the
additional PET/CT imaging study